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.
• diagnostic tests :
• skin testing may be used to detect allergen-specific IgE antibodies. However, with the exception of penicillin, the relevant immunogens (which may be derived from an unidentified drug metabolite or degradation product) are not known for most drugs. Thus, there are no valid in vivo or in vitro diagnostic reagents available for identifying most antibiotic-specific IgE antibodies. Although the parent antibiotic compound may be used in testing by allergy specialists, a negative response on a skin test cannot be interpreted to mean that IgE antibodies are absent^ref. Rather, a negative result may simply indicate insufficient sensitivity of the assay technique or, more likely, that the appropriate drug immunogen was not used in testing. Skin testing is highly accurate for the identification of penicillin allergy, however. The clinically relevant antigenic determinants for penicillin are well characterized and include the important penicillin determinant penicilloyl polylysine and multiple minor determinants. Skin testing is performed with penicilloyl polylysine and either penicillin G diluted to 10,000 U/ml or a mixture of minor determinants that usually includes a 10^–2 M mixture of benzyl penicilloate, benzyl penilloate, and benzyl-n-propylamine^ref. Skin-prick testing with full-strength materials is done first, and if these tests are negative at 15 minutes, they are followed by intracutaneous testing. An increase in the wheal diameter of at least 3 mm (as compared with the negative control) in the presence of erythema constitutes a positive test. < 20% of patients who report a history of penicillin allergy have detectable penicillin-specific IgE antibodies at the time of testing^{ref1, ref2, ref3}. Negative skin testing indicates that the previous reaction was not IgE-mediated or that the antibodies are no longer present; in either case, penicillin can be administered again with minimal risk of an immediate reaction (< 4%, an incidence similar to that in the general population^{ref1, ref2}). Although penicilloyl polylysine has recently become unavailable commercially owing to manufacturing issues related to the production of a low-volume product, production is expected to resume in the future.
• other testing : skin testing is not predictive for drug reactions that are not mediated by IgE. In such cases, other tests may be useful but must be performed during or soon after the reaction. A positive Coombs' test indicates cell-bound antibodies (e.g., penicillin-induced hemolytic anemia), and low complement levels may indicate the involvement of the complement cascade (e.g., minocycline-induced serum-sickness–like reaction^ref). Levels of serum tryptase, a mast-cell–specific neutral protease that indicates systemic mast-cell activation, have been shown to be elevated for several hours after anaphylactic drug reactions^ref. Drug-specific T cells, which are involved in some hypersensitivity reactions, may be detected with the use of in vitro lymphocyte transformation tests, which are widely used in Europe but not approved for use in the USA. This test involves mixing lymphocytes from the patient with the drug that elicited the reaction. If drug-specific T cells are present, a proliferative response may result; proliferation, as measured by the incorporation of tritiated thymidine in the presence of the drug, is compared with that in the absence of the drug^ref. A positive test result indicates that the patient has been sensitized to the drug. However, sensitization may be present even in the absence of any clinical manifestations, and positive test results have been demonstrated in both immediate and delayed antibiotic-induced reactions caused by b-lactam drugs, sulfonamides, and quinolones^ref. Until this test is further validated, it is best considered a research tool. Provocation testing, which involves the administration of approximately three to six increasing doses of a drug up to the usual daily dose, may be used to confirm drug hypersensitivity^ref. However, provocation testing carries a clear risk of a reaction similar to the previous immediate hypersensivity reaction, although subsequent reactions are generally milder and briefer than the original reaction. In one study, the overall rate of such reactions during provocation testing was 17.6%^ref. Thus, such testing should be performed only by experienced personnel in a setting in which equipment for cardiopulmonary resuscitation is available.
Treatment :
• drug desensitization : for reactions that are presumed to be mediated by IgE, drug desensitization may be performed if the implicated agent is required for treatment^ref. Desensitization is performed by a person with appropriate training, typically in a hospital setting. It involves the administration of increasing amounts of the antibiotic slowly over a period of hours until a therapeutic dose is reached. The typical starting dose is in micrograms; the route of administration may be oral or intravenous, but the oral route appears to be associated with fewer reactions. Doses are doubled every 15 to 30 minutes; therapeutic levels can be obtained in most cases within 4 to 5 hours^{ref1, ref2}. The patient is monitored closely throughout the procedure, and antihistamines and inhaled -agonists are given for urticarial reactions and bronchospasm, respectively. If a mild reaction (e.g., flushing or urticaria) occurs, the procedure may resume at the last tolerated dose; if a reaction is severe (hypotension or severe bronchospasm), the procedure should be aborted and an alternative antibiotic selected. The mechanism by which clinical tolerance is achieved is unclear, but it is thought to involve antigen-specific mast-cell desensitization^ref. Since maintenance of a desensitized state requires the continuous presence of the drug, desensitization must be repeated if the antibiotic is required again later. In a recent retrospective report^ref, desensitization for IgE-mediated drug allergy was successful in 43 of 57 cases (75%). Eleven desensitizations (19%) were complicated by severe allergic reactions, either during the procedure (anaphylaxis) or days after its completion (serum sickness); three were terminated for reasons other than allergic reactions. In most cases of failed desensitization, the drug reaction did not appear to be solely mediated by IgE. Desensitization appears more likely to fail in patients with cystic fibrosis^{ref1, ref2}.
• graded challenge : for reactions that are not considered to be mediated by IgE, management depends on the clinical manifestations of the previous reaction. For maculopapular eruptions, the specialist may consider a graded drug challenge, which is equivalent to provocation testing^ref. Initial starting doses are generally higher than those used for desensitization (milligrams vs. micrograms), and the interval between doses varies, ranging from hours to days or even weeks. The patient is monitored for adverse reactions, which are most commonly cutaneous. The decision whether to discontinue an antibiotic if a reaction occurs depends on the nature of the reaction; bullous lesions or those involving mucous membranes warrant withdrawal of the drug, whereas it may be reasonable to treat through milder reactions, such as maculopapular eruptions, with the use of antihistamines, corticosteroids, or both as needed. During drug readministration, repeated hypersensitivity reactions (morbilliform eruptions, fever, or both) have been noted in 58% of patients with the acquired immunodeficiency syndrome who have had previous reactions to sulfamethoxazole^ref. Several graded-challenge procedures have been used successfully in such patients. An analysis of several studies showed that readministration of sulfamethoxazole with the use of an incremental-dosing regimen permitted the use of the drug in > 75% of treated patients^ref. Repeated administration is contraindicated, however, after any life-threatening reaction that is not mediated by IgE (e.g., drug-induced hemolytic anemia, immune-complex reactions, the Stevens–Johnson syndrome, and toxic epidermal necrolysis).
• cephalosporin in patients with penicillin allergy : penicillins and cephalosporins share a b-lactam ring structure, making cross-reactivity a concern. Although a rate of cross-reactivity of > 10% has been reported, this figure must be interpreted with caution since it is based on retrospective studies in which penicillin allergy was not routinely confirmed by skin testing, and at least some of the reactions were probably not immune-mediated^ref. Available data, although based on small numbers, suggest an increased risk of cephalosporin reactions among patients with positive results on penicillin skin tests. In a review combining data from 11 studies of cephalosporin administration in patients with a history of penicillin allergy^ref, cephalosporin reactions were found to have occurred in 6 of 135 patients with positive skin-test results for penicillin allergy (4.4%), as compared with only 2 of 351 with negative skin tests (0.6%). Whereas most patients who have a history of penicillin allergy will tolerate cephalosporins, indiscriminate administration cannot be recommended, especially for patients who have had life-threatening reactions^ref. Among 12 cases of fatal anaphylaxis caused by antibiotics in the UK from 1992 to 1997, 6 cases occurred after the first dose of a cephalosporin, and 3 of the 6 patients were known to have penicillin allergy^ref. For patients with a history of penicillin allergy who require a cephalosporin, treatment depends on whether the previous reaction was mediated by IgE^{ref1, ref2}. Skin testing is warranted if the reaction was consistent with an IgE-mediated mechanism or if the history is unclear. In one study, one third of patients with positive results on skin tests had unclear or vague histories of penicillin allergy^ref. If testing is positive and a cephalosporin is considered necessary, then desensitization should be performed with the use of the particular cephalosporin chosen for treatment. A possible alternative is to perform a graded challenge with the cephalosporin^ref, but the risk of anaphylaxis, although low, must be recognized^ref. If the history is inconsistent with an IgE-mediated mechanism, it is considered safe to initiate a graded challenge without previous skin testing.
• sulfonamide allergy : for patients who have a history of allergy to sulfonamide antibiotics, concern has been raised about the use of other sulfonamide-containing drugs (diuretics, sulfonylureas, and celecoxib). However, sulfonamide antimicrobial agents (sulfamethoxazole, sulfadiazine, sulfisoxazole, and sulfacetamide) differ from other sulfonamide-containing medications by having an aromatic amine group at the N4 position and a substituted ring at the N1 position; these groups are not found in nonantibiotic sulfonamide-containing drugs. Thus, despite product-labeling warnings, cross-reactivity between these two groups of sulfonamides is believed to be unlikely^{ref1, ref2}. In a large observational study^ref, patients with a history of allergy to sulfonamide antibiotics had an increased risk of an allergic reaction to nonantibiotic sulfonamides, as compared with patients without such a history (adjusted odds ratio, 2.8; 95% confidence interval, 2.1 to 3.7), and were even more likely to have a reaction to penicillin (adjusted odds ratio, 3.9; 95% confidence interval, 3.5 to 4.3). These results suggest that the association between an allergy to sulfonamide antibiotics and subsequent reactions to nonantibiotic sulfonamide drugs is probably attributable to a predisposition to allergic reactions in general, as opposed to cross-reactivity between sulfonamide-containing antibiotics and nonantibiotic drugs^ref. However, the results must be interpreted with caution, given the retrospective design and the use of diagnosis codes to categorize reactions, which probably resulted in some misclassification of nonallergic reactions as allergic reactions.
• Areas of uncertainty : the mechanisms underlying antibiotic allergy have not been clearly elucidated. This understanding is needed to facilitate the development of better diagnostic tools and drugs that are less immunogenic. Better understanding is needed of factors mediating individual susceptibility to allergic reactions to antibiotics. A few studies have evaluated the role of major-histocompatibility-complex polymorphisms in the predisposition of patients to drug reactions^ref1,ref2, but these findings need to be confirmed and expanded. Some patients have reported adverse reactions to many chemically unrelated antibiotics. The existence of the so-called multiple drug allergy syndrome is controversial^{ref1, ref2}, and accepted diagnostic tests are needed to document drug allergy in these patients.
Guidelines : the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Task Force on Practice Parameters for Allergy and Immunology have developed practice guidelines for the management of drug allergy^{ref1, ref2} on the basis of evidence and expert opinion. The recommendations in the present review are consistent with these guidelines
• procaine
• oxybuprocaine / benoxinate
• lidocaine
• acetylsalicylic acid
• myorelaxants
• Aculeata (Hymenoptera) insect stings (21%) : often cause also DIC

Epidemiology : an earlier study of food-related anaphylaxis in the emergency department (ED) suggested low concordance with national guidelines for anaphylaxis management. To extend these findings, we performed a chart review study to describe current ED management of insect sting allergy. The Multicenter Airway Research Collaboration performed a chart review study in 15 North American EDs. Investigators reviewed 617 charts of patients with insect sting allergy. Patients were identified by using International Classification of Diseases, 9th Revision, codes 989.5 (toxic effect of venom), 995.0 (other anaphylactic shock), and 995.3 (allergy, unspecified). The cohort was 42% female and 61% white, with a mean age of 36 ± 19 years. In this cohort, 58% had local reactions, 11% had mild systemic reactions, and 31% had anaphylactic reactions, as defined by multisystem organ involvement or hypotension. Among patients with systemic reactions (mild or anaphylaxis), most (75%) were stung within 6 hours of ED arrival. While in the ED, 69% of systemic reaction patients received antihistamines, 50% systemic corticosteroids, and 12% epinephrine. Almost all systemic reaction patients (95%) were discharged to home. At ED discharge, 27% (95% CI, 22% to 33%) of systemic reaction patients received a prescription for self-injectable epinephrine. Only 20% (95% CI, 15% to 26%) had documentation of referral to an allergist. Although guidelines suggest specific approaches for the emergency management of insect sting allergy, concordance with these guidelines appears low in patients with a severe insect sting reaction^ref.
• Apoidea
• Apidae
• Apis spp. (honeybees)
• Apis mellifera

=> Api m 1
=> Api m 2
=> Api m 3
• Bombus (bumblebees)
• Bombus terrestris

=> Bom t 1
=> PL-A₂ (> 90%), hyaluronidase, mellitin, acidic phosphatase
• Formicidae
• Myrmeciinae
• Myrmecia
• Myrmecia pilosula

=> Myr p 1
=> Myr p 2
• Solenopsis
• Solenopsis geminata (tropical fire ant)

=> Sol g 4
• Solenopsis invicta (red imported fire ant)

=> Sol i 2
=> Sol i 3
=> Sol i 4
• Solenopsis richteri (black imported fire ant)

=> Sol r 2
=> Sol r 3
• Vespoidea
• Vespidae
• Polistinae
• Agelaia
• Agelaia pallipes pallipes

=> agelotoxins (= PL-A₂)
• Polispes
• Polistes annularis (paper wasp)

=> Pol a 1
=> Pol a 2
=> Pol  a 5
• Polistes dominulus (European paper wasp)

=> Pol d 5
• Polistes exclamans (paper wasp)

 => Pol e 5
• Polybia
• Polybia paulista

=> polybitoxins (= PL-A₂)
• Vespinae
• Vespa
• Vespa crabro (European hornet)

=> Vesp c 5
• Vespa mandarinia (hornet)

=> Vesp m 5
• Vespula
• Vespula flavopilosa (yellow jacket, wasp)

=> Ves f 5
• Vespula germanica

=> Ves g 5
• Vespula maculifrons (Eastern yellow jacket)

=> Ves m 1
=> Ves m 5
• Vespula pensylvanica (Western yellow jacket)

=> Ves p 5
• Vespula squamosa (Southern yellow jacket)

=> Ves s 5
• Vespula vulgaris

=> Ves v 1
=> Ves v 2
=> Ves v 5
• Vespula vidua

=> Ves vi 5
=> PL-A₂, hyaluronidase
Epidemiology : the earliest reported death from an allergic reaction to a stinging insect was that of King Menes of Egypt, who died in 2641 B.C., purportedly as the result of a wasp or hornet sting. Currently, there are at least 40 fatal stings per year in the United States, and it is likely that many others go unrecognized^ref
Primary prevention : if you are allergic to bee stings, you should limit gardening and lawn mowing, and you should not wear perfumes, hair sprays or bright clothing that attracts insects. Alcoholic drinks have been described as triggering or initiating anaphylactoid reactions^ref. Although little is known about the pathogenesis of these reactions^ref, wine contains many biologic and chemical components derived from grapevines, yeast, bacteria, and insects (including those of the order Hymenoptera) that might explain the observed symptoms^{ref1, ref2, ref3}
Prognosis : a clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings (3% vs. 17%) even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults.
• patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (32%) than if they had received venom immunotherapy (5%)
• in patients who had been treated and who had a history of mild (cutaneous) systemic reaction (i.e., one with only cutaneous manifestations), no subjects who received stings had a systemic reaction^ref.
• iodine-based constrast agents
• industrial chemicals, natural rubber latex (NRL) and rubber products used by healthcare workers
• allergen shots during allergen-specific immunotherapy
• homologous IgA administered to patients with IgAD which have anti-IgA Ab
• hydatid rash : an urticarial eruption which sometimes follows tapping or rupture of a hydatid cyst
• hydatid toxemia : toxemia with urticaria caused by hydatid fluid which has escaped into the peritoneal cavity.
Pathogenesis => symptoms
Diagnosis :
• [histamine]_serum (within 1 hour)
• [b-tryptase]_serum (within 5 hours)
Differential diagnosis :
• other shock syndromes
• gastric carcinoid syndrome
• medullary carcinoma of the thyroid
• systemic mastocytosis
• M2 Baso leukemia
Therapy :
• epinephrine (1:1000, 0.2-0.5 mL s.c. or i.m. every 20' if severe; if systemic arterial hypotension is difficult to treat : 1:10,000, 2.5 mL i.v. every 5-10'; 0.33 mg in 30 mL in peoples weighing > 45 kg; 0.165 mg in 30 mL in peoples weighing < 45 kg) : usually 2.05 mL portable self-injectable syringes are available. Inject into thigh (not on buttocks or other places to prevent i.v. injection) and maintain needle within muscle for 10 sec => massage for 10 sec
• proximal lace and in situ vasoconstrictor (epinephrine 1:1,000, 0.2 mL) to prevent allergen spread in bloodstream after stings
• hydroelectrolyte therapy to maintain blood volume
Prognosis : with appropriate treatment, mild cases of anaphylaxis usually resolve within a few hours. If untreated, anaphylaxis can cause death within minutes to hours.
• allergic skin diseases can be triggered by :

Aetiology :
• inhaled allergens
• ingested allergens
• injected allergens
• contact allergens : cercarial dermatitis / diggers' itch / cutaneous schistosomiasis / schistosome dermattis / swimmers' dermatitis : a severely pruritic papular eruption occurring in those who swim or wade in certain bodies of fresh or salt water, due to hypersensitivity to the cercariae of schistosomes in the water that penetrate the skin and die without gaining access to the circulation and deeper tissues, evoking an inflammatory reaction.
They can be :
• acute (lasting few days; prevalence : 10-20%)
• chronic (lasting > 6 weeks : in 50% it lasts > 6 months)
Varieties :
• atopic dermatitis (AD) / atopic eczema/dermatitis syndrome (AEDS) / eczematous dermatitis / Besnier's prurigo

Epidemiology : 2% prevalence (10-20% of infants : e.g. 23% in Norwegian babies); onset in the first year of life in 50% of cases (usually between month 2 and 6), in the first 5 years in 80%
Aetiology :
• intrinsic : SNPs in
• atopic dermatitis 1 (ATOD1)
• atopic dermatitis 2 (ATOD2)
• atopic dermatitis 3 (ATOD3)
• atopic dermatitis 4 (ATOD4)
• atopic dermatitis 5 (ATOD5)
• atopic dermatitis 6 (ATOD6)
• expressed in T-cells and eosinophils in atopic dermatitis (ETEA)
• IgE
• FceRII
• trypsin
• IL-4 (-589C/T)
• IL-4Ra (Ile50Val)
• TP (795C/T)
• extrinsic : persistence of atopic eczema is the stimulation of the immune system by SAg produced by Staphylococcus aureus. Specific immune responses against a variety of environmental allergens are also implicated in the pathogenesis of AD.
Pathogenesis : the primary reaction is a T_h1 reaction and it is now thought that a T_h2 response is mediated via high affinity IgE receptors on Langerhans cells. Increased levels of the T_h2-type cytokine IL-4 can be detected in both affected and unaffected skin^ref. Production of T_h1-type cytokines, such as IFN-g, and cytotoxic T-cell functions are also impaired in patients with AD^{ref1, ref2}. T-cell homing might be dysfunctional in these patients as well. In mice, the generation of T_h1-type, but not T_h2-type, cytokines, is associated with a skin-homing phenotype^ref. The presence of skin-homing T_h2 cells in atopic patients might represent an uncoupling of this association^ref. Surprinsingly, even innate immunity might be impaired in these patients^ref. The production of IL-18 is also increased in AD^ref, and keratinocytes from patients with AD produce a different array of cytokines and chemokines than do keratinocytes from non-atopic individuals^{ref1, ref2, ref3}. Reduced cutaneous response to tuberculin, candidin, streptokinase-streptodornase when injected intradermally. Reduced in vitro response of peripheral blood lymphocytes to PHA and ConA, reduced chemotaxis of neutrophils and monocytes.
Symptoms & signs :
• in babies (infantile eczema) : itchy, thickened, fissured skin evolving to exudating and crustous plaques, most often in the folds of the arms and backs of the knees. It tends to come and go, and usually improves with age.
• in older children and adults (lichen simplex chronicus / circumscribed or localized neurodermatitis) : one or more clearly defined patches produced by chronic rubbing of the skin chiefly on the flexural surfaces (flexural eczema), especially on the antecubital and popliteal areas, face (eyelids), nuchal region, behind the ears, extremities (wrists, hands, ...), scrotum, vulva, and perianal region
• nummular eczematous dermatitis
• exudative discoid and lichenoid dermatitis / oid-oid disease / Sulzberger-Garbe syndrome : a form of neurodermatitis occurring predominantly in middle-aged or older men of Jewish extraction, characterized by intense pruritus with exudative, weeping discoid and oval patches scattered irregularly over most of the body, many of which are of the eczematous type and undergo lichenification, or they may resemble lesions seen in various other cutaneous disorders such as mycosis fungoides or lichen planus.
Intense prurigo => scraping => secondary lesions and infections (dermatitis vegetans / pemphigus vegetans, Hallopeau type : development of exuberant hypertrophic granulation tissue that may erode to form ulcers. A variant involving the oral mucosa and associated with ulcerative colitis or other gastrointestinal disturbance is known as pyostomatitis vegetans); perioral pallor, additional skin fold under lower eyelid (Dennie-Morgan fold), accentuation of palmar folds, anomalies of cutaneous vascular responses.
Therapy : avoid warm baths and excessive soap use, antibacterial baths; immunotherapy (desensitization) is not effective, while anti-histamine drugs are effective only thanks to sedative properties.
Prognosis : 90% of babies heal after 12 years, 80% develop allergic rhinitis or asthma. Patients with either active or quiescent atopic dermatitis are at risk after immnuization with smallpox vaccine for the development of eczema vaccinatum.
Web resources : Atopic dermatitis images
• urticaria / hives / wheal-and-flare

Epidemiology : 20% at some time in life, with the greatest number of episodes occurring in people aged 20 to 30.
Aetiology :
• inhaled allergens
• ingested allergens
• injected allergens
• harara / urticaria multiformis endemica : an allergic skin reaction caused by bites of the sand fly Phlebotomus papatasii, seen in the Middle East, and characterized by urticarial and inflammatory papules and blisters. Immunity usually follows the initial exposure
• reactions to mosquito bites are immunological in nature, with the involvement of IgE-, IgG- and T lymphocyte-mediated hypersensitivities. Acquired desensitization to mosquito saliva may occur during childhood and adolescence or during long-term exposure to mosquito bites. Due to the lack of salivary preparations, allergic reactions to mosquito bites are underdiagnosed and undertreated. Recombinant mosquito saliva allergens with biological activity are being developed. These recombinant allergens will significantly improve diagnosis of mosquito allergy and eventually will also improve specific immunotherapy for patients with systemic reactions to mosquito bites^ref. Mosquito bite exposure results in a variety of reactions and secondary complications. Clinical hypersensitivity manifests primarily as local reactions with anaphylaxis being a very rare event. Risk factors for more severe local reactions include immunodeficiency, young children and visitors to an area with new exposure to indigenous mosquitoes. Necrotic skin reactions to mosquito bites have been associated with a newly recognized hemophagocytic syndrome in predominantly oriental populations. Diagnostic and therapeutic agents in the clinical management of mosquito hypersensitivity remain limited, but recent discovery of 3 recombinant proteins (rAed a 1, rAed a 2, rAed a 3) shared by several mosquito species promise to be more specific skin test antigens for the future^ref.
• physical causes
• (white) dermographism / dermatographism / dermographia is  the most common form of physical urticaria (prevalence : 1-4%, expecially between age 10 and 30, average lasting < 5 years). A single stroke or scratch of the skin produces a localized wheal with surrounding red flare. It should not be confused with black dermatographism, in which black or greenish streaking of the skin is caused by deposit of fine metallic particles abraded from jewelry by various dusting powders.
• familial dermographism
• cold urticaria
• familial cold urticaria (FCU) / familial cold autoinflammatory syndrome (FCAS)
• hot urticaria (cholinergic urticaria) : 1-2 mm-wide nettle-rash
• familial localized hot horticaria
• sunlight urticaria
• aquagenic (water contact) urticaria (sometimes due to polycythemia vera)
• dermodistortive urticaria (DDU) : autosomal dominant disorder consisiting of appearance of pruritic, erythematosus, edematous, cutaneous swelling confined to the stimulated area within several minutes after stimuli that vibrate or stretch the skin in a repetitive manner, disappearing within 1 hour. Extensive stimulation causes not only local urticaria but also a systemic response of faintness, headache, and facial erythema.
• vibration urticaria
• stretch urticaria
• stress urticaria
• chronic idiopathic urticaria (30-45%) :
• chronic autoimmune urticaria (40-50%) : association with antithyroid antibodies and is caused by IgG antibody to the a subunit of FceRII (35-40%), usually reactive with unoccupied IgE receptors, or IgG antibody to IgE (5-10%). Complement activation augments histamine secretion by release of C5a. The IgG subclasses that appear to be pathogenic are IgG₁, IgG₃, and, to a lesser degree, IgG₄, but not IgG₂.
• chronic idiopathic urticaria (50-60%)
Patients in both groups may have concomitant angioedema (approximately 40%).
Pathogenesis : histology of chronic urticaria (both subtypes) reveals a perivascular non-necrotizing infiltrate of CD4⁺ lymphocytes consisting of a mixture of T_h1 and T_h2 subtypes, plus monocytes, neutrophils, eosinophils, and basophils. These cells are recruited as a result of interactions with C5a, cell priming cytokines, chemokines, and adhesion molecules.
Therapy for patients with severe disease involves the use of high-dose hydroxyzine or diphenhydramine when nonsedating antihistamines are ineffective, supplemented by H₂ antagonists and cysLT₁ antagonists. The most severe patient may require protracted treatment with low-dose alternate-day steroid or cyclosporine A. Cyclosporine can be steroid-sparing when side effects are encountered or when use of steroids is relatively contraindicated. Careful monitoring of blood pressure, BUN, creatinine, and urinalysis is required^ref.
• pseudoimmunologic urticaria from pseudoallergic reactions (PAR)
Symptoms & signs : asymmetric bump (itching, raised, rounded or oval exanthema, sometimes confluent and erythematous; a.k.a. pomfo in Italy) due to vasodilatation of capillaries and venules in the upper layers of any area of dermis (usually limb extremities or face). Nettle rash is urticaria in domestic animals as an allergic reaction to nettles
Prognosis : lasting < 72 hours (usually 8-12 hours), may appear every 24 to 72 hours if the patient continues to be exposed
• angioedema : asymmetric, nonerythematous, not raised, not itching, painful ("burning"), diffuse (usually on face, tongue, limbs or genital areas) exanthema due to vasodilatation of blood vessels in any area of skin and subcutaneous tissue (usually eyes and lips), sometimes accompanied to mucosal edema, which may cause lethal mechanical obstruction of URT and abdominal pain.

Aetiology :
• vibratory angioedema (VA)
• ACEI-associated angioedema : there is a defect in a non-ACE, non-kininase I, dipeptidyl peptidase IV (DPPIV) pathway of bradykinin degradation
Pathogenesis : only 66% subjects with allergen-specific IgE develop symptoms
Diagnosis :
• anamnesis (exposure-symptoms relations)
• objective examination (e.g. rhinoscopy)
• laboratory examinations
• epicutaneous tests / skin tests (up to 7-8 test per forearm, each separated by at least 2-3 cm)
• scratch test / skin prick test (SPT) (1 drop of a solution 1 mg / mL) : 45° intraepidermal injections of several different allergens with a 1-mm long blade, lifting epidermis (simulating physiological entry way : high specificity, low sensitivity), often in a grid pattern on the back. Peak positivity at age 15-25 years; in asymptomatic babies positivity predicts a 50% risk of developing allergic rhinitis and 5% risk of developing allergic asthma in the next 5 years
• intracutaneous or intradermal test : a skin test in which the antigen is injected below the skin (0.01 mL of allergen solution 1 ng / mL - 1 mg /mL) (low specificity due to aspecific injury; sensitivity 100-fold greater than for prick test)
Positive control by using histamine 1% only.
Negative control by using allergen solvent (phenol 0.5% saline) only
After 15-20' a comparison between the nettle-rash at the test place and at positive control place is done.
False negativity may be due to :
• inactive allergens
• contemporaneous therapy with anti-histamine or steroidal drugs (stop taking antihistamines and other medications for at least 3 to 7 days before testing)
False positivity may be due to :
• dermatographism (detected by negative control)
• irritants in solvents (detected by negative control)
• wrong execution
• excessive injury
• confluence
Side effects : rare severe local or systemic hypersensitivity within 30'.
Positivity can't predict if hypersensitivity will be local or systemic.
• Prausnitz-Küstner (P-K) reaction (1921) is the passive transfer of cutaneous atopy through serum transfusion. Küstner was extremely sensitive to certain fish : an in vivo test was done by Prausnitz in which he took Küstner's serum and injected a small amount intracutaneously in a volunteer. 24 hours later, fish extract was injected intracutaneously into the volunteer at the same site. An immediate wheal and flare reaction occurred at the site because Küstner's serum contained IgE antibodies that bound to recipient mast cells. The P-K test is very rarely used today because of the possibility of transferring disease from one person to another (hepatitis, for example), and because of in vitro tests that are adequate. The P-K test may be used to determine whether a young child has a particular allergy and the direct skin test is contra- indicated, or in adults with a disseminated skin disease where it may be difficult to administer the test.
• plasma IgE dosage
• total IgEs : paramagnetic liquid- or solid-phase sandwich EIA uses anti-IgE Ab
• specific IgEs :
• solid-phase Ag radioallergosorbent test (RAST) uses radiolabeled anti-IgE Ab
• enzyme allergosorbent tests (EAST)
Predictive value : 80%, unrelated to severity.
• cytology (to detect eosinophilia)
Treatment :
• primary prevention (sometimes not practiceable, e.g. for unreplaceable drugs or allergens in workplace)
• in patients with a history of severe allergic reactions, a medical-alert ID necklace or bracelet can save valuable time in identifying the problem
• cover pillows and mattress with plastic
• cover overstuffed furniture
• eliminate wool from bedding
• remove domestic animals from the house
• air-condition the house
• immunotherapy
• allergen hyposensitization by inducing peripheral tolerance) : usually ineffective if a previous anaphylaxis occurred. It is recommended in atopic adults (risk of anaphylaxis : 60%), but not in babies with urticaria or angioedema (risk of anaphylaxis : 10%; atopy usually disappear with age). Increasing doses each week up to a maintaining dose of about 100 mg / mL (for drugs up to therapeutic dose), followed by challenging every 2-3 months for 3 to 5 years (in case of anaphylaxis, even during immunotherapy, or atopy to bee venom). It cannot prevent food allergies.
• mAbs
• chemotherapy :
• p.o. or i.v. nonsedative, hydrophilic or second generation H₁ antagonists (registered) : peak after 2-3 hours, liver catabolism => urine, effective for 4-6 hours (pyperazines and piperidines for 6-24 hours). Side effects from piperidines : inhibition of slow K⁺ channels => polymorphic ventricular tachycardia if associated to macrolides or antimycotics which compete for catabolyzing enzymes.
• p.o. or i.v. H₂ antagonists (?)
• H₄ antagonists (preclinical)
• cysLT₁ antagonists (registered)
• cysLT₂ antagonists (preclinical)
• p.o. or i.v. GR agonists. Side effects : atrial fibrillation, especially with new courses of therapy^ref
• DP₁ antagonists (phase I and II clinical trials)
• DP₂ / CRTH2 / GPR44 antagonists (preclinical)
• b-tryptase inhibitors (phase I clinical trials)
• mast cell ion channel blockers (preclinical)
• mast cell signalling inhibitors (phase I clinical trials)
• neuropeptide antagonists (phase I and II clinical trials)
• SLIT (phase III clinical trials)
• peptide-based IT (phase I clinical trials)
• CpG ISS (preclinical and phase I clinical trials)
• CpG-allergen conjugate (phase II clinical trials)
• anti-IgE mAbs
• IgE peptides (preclinical)
• IL-4 antagonists/anti-IL-4 mAbs (phase I clinical trials; phase II clinical trials for soluble receptor)
• IL-13 antagonists/anti-IL-13 mAbs (phase I clinical trials)
• anti-CCL11 / eotaxin mAbs (phase I clinical trials)
• CCR3 antagonists (phase I clinical trials)
• mycobacterial vaccines (phase I clinical trials)
• probiotics (phase II clinical trials)
• anti-VLA-4 antagonist mAbs (phase II clinical trials)
• P-selectin antagonists (phase I clinical trials)
• E-selectin/ICAM-1 antagonists (phase I clinical trials)
• for allergic rhinitis and bronchial asthma only :
• mast cell stabilizers
• inhaled (p.o. only if age < 5) b₂ agonists (tachyphylaxis for prophylaxis > therapy)
• short-acting b₂ agonists (SABA) : effective since 2-3' after administration for 2-6 hours
• long-acting b₂ agonists (LABA) : effective since 20" after administration for > 12 hours
• slow-release selective PDE4 inhibitors (12-24 hours) (phase II clinical trials). Side effects : atrial fibrillation, especially with new courses of therapy^ref
• antivagal drugs (M₁ antagonists) :
• short-acting (3-6 hours)
• long-acting (24 hours)
• Ado receptors antagonists
• NKs antagonists
• anti-Fce mAbs
• AP-1 inhibitors
• anticongestant : a agonists
Inhalatory therapy can be administered via :
• nebulizers (used expecially in reacutizations)
• pressurized metered-dose inhaler (pMDI)
• keep the inhaler at 15 cm from mouth
• deep expiration
• inspire slowly and deeply
• keep breathing for 30"
• expire from nose
Particles have a 2 < mass median aerodynamic diameter (MMAD) < 4 mm
• dry powder inhaler (DPI) (Turbohaler, Turbuhaler) don't require ventilomotory coordination but may cause local irritation due to high deposition in oral cavity.
Spacers can be used to avoid dispersion in environment. Wash oral cavity after treatment : topical GR agonists may cause candidiasis.
Tertiary prevention
Web resources :
Allergen sequences at ExPASy
General information on allergy and allergens at HON
List of allergens
IUIS/WHO Allergen Nomenclature Subcommittee
Allergen sequence database in Biotechnology Information for Food Safety (BISF) Database
Structural Database of Allergenic Proteins (SDAP)

 
Allergy Society of South Africa (ALLSA)
• Allergy Basics Center
• Allergy and Clinical Immunology (ACI) International On-line
• Asthma and Allergy Foundation of America (AAFA)
• Allergy and Asthma Disease Management Center (AADMC) at AAAAI
• AllergyImmunoLinx
• Allergy Web
• Calgary Allergy Network
• Cytokines in allergic disease
• European Federation of Asthma and Allergy Associations (EFANET)
• Immunologic basis of allergic disease
• Mission : Allergy
• National Institute for Allergy & Infectious Diseases (NIAID)
• Publications
• Nederlandse Vereniging voor Allergologie (NVvA)
• Polskie Towarzystiva Alergologiczne (PTA)
• Schweizerisches Institut für Allergie- und Asthmaforschung (SIAF)
• Svenska Föreningen För Allergologi (SFFA)
• World Allergy Organization (WAO)
• Journals
• Allergologie (impact factor 2001 : 0.278)
• Allergology International
• Allergy (impact factor 2001 : 2.552)
• Clinical and Experimental Allergy (impact factor 2001 : 3.826)
• Pediatric Allergy and Immunology (impact factor 2001 : 1.753)
• pseudoallergic reactions (PAR) (if at systemic level : anaphylactoid reactions)
• mediators release from mast cells and basophils induced by :
• IL-3
• hypoosmolality
• complement-mediated hypersensitivities : anaphylotoxins C3a, C4a (weak), and C5a can induce degranulation
• PL-A₂ in Hymenoptera venoms
• radiocontrast enhancement media (Urografin, ... )
• patients taking ACEI who are undergoing hemodialysis with polyacerylonitrile AN69 membranes or plasma fractionation with ethylene vinyl alcohol and acrylic copolymers
• (poly)basic substances
• amides
• amidines
• quaternary ammonium compounds
• pyridinium compounds
• piperidines
• alkaloids
• d-tubocurarine
• morphine
• noscapine
• antibiotic bases
• succinylcholine
• talmadol
• aminotrizoic acid
• compound 48/80 : this is a mixture of low-molecular-weight polymers of p-methoxy-N-methylphenethylamine, of which the hexamer is most active.
• polymixin B
• mastoparan
• nephilatoxins
• peptide 401
• certain carbohydrate plasma expanders (Emagel, ...)
• Ag
• Hg
• vancomycin : "red man syndrome"  is an infusion-related reaction peculiar to vancomycin^ref. It typically consists of pruritus, an erythematous rash that involves the face, neck, and upper torso. Less frequently, hypotension and angioedema can occur. Patients commonly complain of diffuse burning and itching and of generalized discomfort. They can rapidly become dizzy and agitated, and can develop headache, chills, fever, and paresthesia around the mouth. In severe cases, patients complain of chest pain and dyspnea. In many patients, the syndrome is a mild, evanescent pruritus at the end of the infusion that goes unreported. Signs of red man syndrome would appear about 4–10 min after an infusion started or may begin soon after its completion. It is often associated with rapid (<1 hour) infusion of the first dose of vancomycin. The reaction may not be of the same severity with successive exposures, but it can occur for the first time after several doses or with a slow infusion^ref. Delayed reactions at or near the end of a 90 or 120 min infusion have been seen in patients who had been on vancomycin therapy for > 7 days without prior incident^ref. Most of the hospital protocols require vancomycin to be infused over 60 min, as a minimum^{ref1, ref2}. Sporadic reports of red man syndrome following the administration of vancomycin via routes other than intravenously are also on the increase. Red man syndrome has been linked to intraperitoneal and oral administration of vancomycin^ref. Red man syndrome was in the past attributed to impurities found in vancomycin preparations, earning the drug the nickname 'Mississippi mud'. But reports of the syndrome persisted even after improvements in the compound's purity^ref. Studies have shown that an unknown percentage of the population may be prone to releasing a large amount of histamine in response to vancomycin^ref. The hypersensitivity reactions that can arise due to vancomycin are due to its effect on the mast cells. In tissue culture, vancomycin causes degranulation of peritoneal mast cells in rats^ref. The anaphylactic reaction is mediated by IgE. Red man syndrome, an anaphylactoid reaction, is caused by the degranulation of mast cells and basophils, resulting in the release of histamine independent of preformed IgE or complement. The extent of histamine release is related partly to the amount and rate of the vancomycin infusion. Clinical studies have shown that the plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical reactions from immunologic reactions^ref. The most common hypersensitivity reaction associated with vancomycin is red man syndrome. The incidence varies between 3.7 and 47% in infected patients^ref. Studies of vancomycin also show that the most severe reactions occur in patients younger than the age of 40, particularly in children^ref. Other research has found that between 30 and 90% of healthy volunteers receiving vancomycin developed red man syndrome, while only about 47% of those with infections had the reaction^ref. One explanation for these results is that an infection induces some histamine release as part of the natural immune response. Having a higher histamine level to begin with is thought to downregulate vancomycin's effect on mast cells and basophils. It occurs in 5–13% of patients, especially when the infusion is given over < 1 hour^ref. Polk and colleagues^ref observed the reaction during a 1 hour infusion of 1 g vancomycin in 9 of 11 volunteers (82%), which was associated with a rise in plasma histamine levels. No reaction occurred with a 500 mg dose. Healy and colleagues^ref noted symptoms in 8 of 10 volunteers (80%) given 1 g vancomycin over 1 hour, but in only 3 of 10 volunteers (30%) given the same dose over 2 hours. Total histamine release was greater with the faster infusion. Antibiotics such as ciprofloxacin, amphotericin B, rifampicin and teicoplanin^ref can potentially cause red man syndrome. Like vancomycin, they are capable of causing direct degranulation of mast cells and basophils. Red man syndrome is amplified if these antibiotics are combined with vancomycin or with each other^ref. Red man syndrome is also magnified in patients receiving vancomycin and opioid analgesics, muscle relaxants, or contrast dye because these drugs can also stimulate histamine release. The effects of red man syndrome can be relieved by antihistamines.

Pretreatment with hydroxyzine can significantly reduce erythema and pruritus^ref. Administration of diphenhydramine to patients before starting vancomycin infusion (1 g over 1 hour) can prevent the occurrence of red man syndrome with the first dose of vancomycin^ref. Other studies have shown that combining an H₁ receptor blocker with an H₂ receptor blocker such as cimetidine may help to prevent or reduce the risk of red man syndrome^ref. If red man syndrome appears then the vancomycin infusion should be discontinued immediately. A dose of 50 mg diphenhydramine hydrochloride intravenously or orally can abort most of the reactions. Once the rash and itching dissipate, the infusion can be resumed at a slower rate and/or at a lesser dosage. Hypotension will require intravenous fluids and, if severe, vasopressors may be needed. Hypotension can be troublesome if it occurs during anesthesia following the use of vancomycin for surgical prophylaxis^{ref1, ref2}. Therapy with a b-blocker before surgery has been found to be protective against hypotension caused by vancomycin infusion^ref. In summary, each intravenous dose of vancomycin should be administered over at least a 60 min interval to minimize the infusion-related adverse effects^ref. Longer infusion times should be used in patients receiving doses considerably > 1 g vancomycin. Studies have shown that vancomycin is much better tolerated when it is given in smaller and more frequent doses^ref. In clinical situations where prolonged infusion times are often impractical, as in the intensive care unit or an operative setting, especially ambulatory orthopedic or emergency procedures, pretreatment with antihistamines combined with an H₂ receptor blocker can offer protection against this infusion-related reaction with vancomycin^ref.
• Widal-Samter aspirin triad syndrome / aspirin-sensitive asthma / aspirin-induced asthma and rhinitis (AIAR) / aspirin-exacerbated respiratory disease (AERD) : a medical condition consisting of asthma, aspirin sensitivity, and nasal polyposis.

Epidemiology : it occurs in mid-life (twenties and thirties are the most common onset times) and may not include any allergies.
Pathogenesis : leukotrienes synthesis due to NSAID-induced switch from COX to LOX metabolism in individuals with airway hyperresponsiveness (AHR)
Symptoms & signs : most commonly, the first symptom is rhinitis (inflammation of the nose), which might be described as sneezing, a runny nose, or congestion. The disorder typically progresses to asthma, then polyposis, with aspirin sensitivity coming last. The aspirin reaction can be severe, including an asthma attack, anaphlaxis, and uticaria in some cases. Patients typically react to other NSAIDs such as ibuprofen, although acetaminophen is generally considered safe. Anosmia is also typical, as the inflammation reaches the olfactory receptors in the nose. A sufferer who has not yet experienced asthma or aspirin sensitivity might be diagnosed as having non-allergic rhinitis (NAR) or nonallergic rhinitis with eosinophilia syndrome (NARES)
Therapy : nasal steroids, inhaled steroids, and leukotriene antagonists. Occasionally surgery may be required to remove polyps, although they typically recur. Some patients require oral steroids to alleviate asthma and congestion, and most patients will have recurring or chronic sinusitis due to the nasal inflammation.
Aetiology : an anomaly in the arachidonic acid cascade, which causes undue production of leukotrienes, a series of chemicals involved in the body's inflammatory response. When prostaglandin production is blocked by NSAIDS like aspirin, the cascade shunts entirely to leukotrienes, producing the severe allergy-like effects. Leukotriene antagonists and inhibitors such as Singulair, Accolate, and Zyflo show great promise in treating Samter's. A diet low in omega-6 oils (precursors of arachidonic acid), and high in omega-3 oils, may also help. Ongoing study at the Scripps clinic suggests that aspirin desensitization may be beneficial, but the procedure is dangerous due to the risk of anaphlaxis or uticaria, and must be done under medical supervision
Web resources :
• Discussion group at Yahoo
• Aspirin Intolerance and Nasal Polyposis
• amniotic fluid embolism (AFE) / anaphylactoid syndrome of pregnancy
• histamine poisoning results from the consumption of foods that contain unusually high levels of histamine :
• histamine fish poisoning (HFP) : high levels of histamine (> or =50 mg/100 g, but foods containing unusually high levels of histamine may not appear to be outwardly spoiled) in certain spoiled fish containing large amounts of free histidine...
• certain types of scombroid dark meat fish of the families Scombridae (such as mackerels, tuna (Scombridae gen. sp.), albacore (Thunnus alalunga), bonito, skipjack, tuna (Katsuwonus pelamis), marlin) and Scomberesocidae (sauries), which leads to the common usage of the term, "scombroid fish poisoning", to describe this illness.
• certain non-scombroid fish, most notably mahi-mahi / common dolphinfish (Coryphaena hippurus), sardine (Sardinops spp.), yellowtail, herring, anchovy and bluefish. Although rare, cases of whitefish scombrotoxism also have been reported.
Histamine is produced in the muscle tissue of fish if it is kept at a temperature which is too high : Proteus spp., Clostridium spp., Escherichia spp., Salmonella spp. and Shigella spp. histidinase decarboxylate free histidine, which is present in very large quantities in these fish, to histamine / scombrotoxin / pelometoxin. Although some histidine decarboxylating bacteria are present in the normal microbial flora of live fish, most seem to be derived from post-catching contamination on board fishing vessels, at the processing plant or in the distribution system, or in restaurants or homes. Since the concentration of histamine is not evenly distributed through the fish's flesh, not everyone who eats the same fish will become ill to the same extent, and some may not even become ill at all.
Epidemiology : although scombroid poisoning is commoner in nations with a warm water fishing industry, the illness occurs worldwide. Since the complaints are often mild and of short duration, most patients do not seek medical help, and probably few cases are officially reported
Pathogenesis : various hypotheses have been put forward to explain why histamine consumed in spoiled fish is more toxic than pure histamine taken orally, but none has proved totally satisfactory. cis-urocanic acid, like histamine, an imidazole compound derived from histidine in spoiling fish, has recently been recognised as a mast cell degranulator, and endogenous histamine from mast cell degranulation may augment the exogenous histamine consumed in spoiled fish^ref.
Symptoms & signs within 5 to 90 minutes (most 15-60 minutes) after eating the fish : sharp metallic, bitter, or peppery taste to the fish and describe its appearance as honeycombed; skin flushing (typically on the upper half of the body), headache (severe and throbbing), nausea and vomiting, diarrhea, abdominal cramps or epigastric pain and palpitations. Respiratory distress and chest tightness are rare, but bronchospasm and hypotension may occur. Patients taking isoniazid (INH) or monoamine oxidase inhibitors (MAOIs) may have more significant reactions because of histaminase blockade in the GI tract.
Therapy : antihistamines can be used effectively to treat this intoxication.
Prognosis : the duration of symptoms ranges from a few hours to 24 h. Most victims recover but are miserable until then
Prevention : the key to keeping bacterial numbers and histamine levels low is the rapid cooling of dark-meated fish by experienced fishermen after catching and the maintenance of adequate refrigeration during handling and storage until they're cooked by chefs. Despite the fact that sometimes only one person from a group of people eating the same fish becomes ill, and that the clinical complaints resemble an IgE-mediated allergic reaction, the illness is a food-borne intoxication with exogenous histamine. Therefore, patients can safely eat the same type of fish again^ref.
• cheeses, especially Swiss cheese. The control of histamine formation in cheese seems dependent on insuring that histamine-producing bacteria are not present in significant numbers in the raw milk
• red wines
• low molecular-weight aldehydes, ketones, and alcohol in Lycopersicon esculentum (tomato) steam distillate, Fragaria x ananassa (strawberries), food additives, herbs, and white wines
• type II hypersensitivies

Aetiology :
• transfusion reactions (usually AB0 Ags)
• direct (recipient's complete IgM isoagglutinin against donor's RBCs)
• indirect (donor's incomplete acquired IgG againt recipient's RBCs)
• erythroblastosis fetalis or neonatorum / congenital or hemolytic anemia of newborn / hemolytic disease of the newborn (HDN)

Epidemiology :
• Europe : 16% of Europeans are RhD^-. In Caucasian populations about 17% of pregnant women are RhD^-. Of these, around 60% will have a baby who has inherited RhD⁺ blood from its father. 1-2% RhD^- women are at risk of alloimmunization during or immediately after a pregnancy. Over the past 35 years this figure has been cut to about 0.2% by the use of anti-D injections administered in the 28th and 34th week of pregnancy.
• England and Wales an estimated 62,000 babies RhD⁺ babies are born to RhD^- mothers every year. Of these, around 500 develop HDN and 25-30 die of it. About 15 will have permanent developmental problems and 30 will have minor developmental problems
• USA : 15% are RhD^-, although only 5 to 10% of African Americans are RhD^-around 4,000 babies are born each year with HDN
• Africa and Asia : < 1% are RhD^-
• Australia : there are around 25,000 RhD⁺ babies born to about 45,000 RhD^- mothers annually. And this excludes women sensitized through other events such as miscarriages, abortions and invasive procedures. In countries where anti-D is not available or guidelines may not be carefully followed, the risk of RhD alloimmunization is higher than in Australia
Aetiology : incompatibility between the blood group of the mother and that of her offspring
• baby or fetus is CD241 / Rh Ag⁺ (expressed on fetal RBCs since E38) and the mother is Rh^- (the most common and frequently fatal type)
• babies or fetuses of blood groups A and B whose mothers have type O blood; it is much milder than the Rh type because anti-A and anti-B antibodies only occasionally cross the placenta.
• anti-Kell-induced alloimmune HDN : antibody-mediated suppression of erythroid progenitors
Pathogenesis : alloimmunization (sensitization) during labor and secundation (sometimes doesn't occurs as natural anti-AB0 antibodies may destroy fetal RBCs before adaptive immunity to Rh Ag occurs) => production of anti-Ag IgM (which can't cross the placental barrier) within 3-6 months => new pregnancy with same paternal alloantigen on the fetus => transplacental transmission of maternally formed IgG => hemolytic anemia of the fetus or newborn infant =>
• chronic anoxia =>
• cardiac insufficiency
• intense stimulation of both medullary and hepatic hemopoiesis =>
• increased red cell regeneration (nucleated red cells (NRBCs) in the blood)
• liver failure => hypoproteinemia => hydrops fetalis worsened by cardiac insufficiency
• unconjugated hyperbilirubinemia (due to underdeveloped liver catabolism and liver damage) is easily removed by placental circulation as lipophilic
Symptoms & signs : hepatosplenomegaly and jaundice within 24 hours since birth due to loss of placental bilirubin clearance => kernicterus may result. The most severe form is hydrops fetalis
Therapy :
• plasma exchange
• exsanguinotransfusion
• intrauterine transfusion
Prevention :
• anti-Rho(D) mAbs within 72 hrs since alloimmunization (amniocentesis, abortion, extrauterine pregnancy, delivery), independently from fetal-maternal AB0 incompatibility and demonstration of fetal RBCs in maternal blood. Check for development of maternal anti-Rho(D) IgGs 6 months after delivery with indirect Coombs' test : IgGs detected are due to a primary immune response, as exogenous IgGs have been cleared. Administration during pregnancy has no negative effects on either the pregnant ofr the fetus other than a false positivity at direct Coombs' test.
• preimplantation genetic diagnosis (PGD)
Web resources : HDN at University of California
• drug allergies : they subside within several months after removal of the offending agent
• penicillin-inducedhemolytic anemia
• methyldopa-induced hemolytic anemia
• quinidine-induced thrombotic thrombocytopenic purpura
• sulfonamide-induced granulocytopenia
• drug hypersensitivity syndrome (DHS / DIHS) is characterized by a clinical triad of fever, skin rash, and internal organ involvement. Since its first description in relation to dapsone administration, it has been given several descriptive names such as dapsone syndrome, Kawasaki-like illness, drug rash with eosinophilia and systemic symptoms (DRESS), graft-versus-host-like illness, febrile mucocutaneous syndrome, drug-induced delayed multiorgan hypersensitivity syndrome (DIDMOHS), and mononucleosis-like illness

Aetiology : common drugs causing drug hypersensitivity syndrome are dapsone, sulfonamides, sulfasalazine, hydantoin, d-penicillamine, hydrochlorothiazide, cyclosporine, carbamazepine^ref, phenytoin, phenobarbitone, lamotrigine, allopurinol, azathioprine, minocycline, and the anti-retroviral drugs abacavir and nevirapine^ref. The most recent additions to this list include teicoplanin and amitriptyline^{ref1, ref2}. This syndrome characteristically occurs on first exposure to the drug and the reaction classically begins 1-8 weeks into drug therapy^ref. Exogenous precipitating factors for developments of DHS include viruses such as HIV and HHV-6^{ref1, ref2}. Primary HHV-6 infection and HHV6 reactivation have been incriminated in the genesis of DRESS syndrome. Serological tests for HHV-6 should be performed routinely in patients with suspected DRESS syndrome, although uncertainty persists about the link between HHV-6 infection and DRESS syndrome.
Pathogenesis : idiosyncratic reaction. Defective metabolism of the parent compound leading to increased levels of toxic or reactive metabolites is the initial event in the pathogenesis of DHS. The role of these toxic metabolites in an immunologically mediated reaction may be explained by two hypotheses: the hapten hypothesis and the danger hypothesis^ref. According to the hapten hypothesis, reactive drug products bind to tissue macromolecules to form complete immunogens which initiate an immunological process. According to the danger hypothesis, oxidative cell damage caused by reactive drug metabolites leads to release of cytokines that warn the immune system of cellular stress and damage. These signs of danger promote an immune response to eliminate these modified, potentially damaged and dangerous cells
Symptoms & signs : flu-like syndrome with a pruriginous maculopapular erythema initially involving the face, trunk, and proximal limbs; a fever of 41°C; and enlargement of the liver, spleen, and several peripheral lymph nodes
Laboratory examinations :
• marked eosinophilia (9300/ml), lymphocytosis, hyperbasophilic cells, and severe inflammation
• drug-induced lymphocyte stimulation tests
• indirect immunofluorescence assay for HHV-6 in affected skin
• rarely transient hypogammaglobulinemia
Prognosis : DRESS syndrome continues to carry a high mortality rate of about 10%.
Pathogenesis : T_h2 polarization
• type III hypersensitivities

Aetiology :
• hypersensitivity pneumonitis (also type IV hypersensitivity)
• vasculitides with main cutaneous involvement

Pathogenesis : deposition of immune complexes containing alloantigens on cutaneous postcapillary venulae > arteriolae and capillaries, nuclear fragment of neutrophils (leukocytoclasia => cutaneous leukocytoclastic vasculitides (LCV)), RBC extravasation => palpable purpura
• (classical) serum sickness

Aetiology : 7-10 days after the first (or 2-4 days after the second) massive parenteral injection of heterologous proteins (heterologous antiserum, blood transfusion or immunotherapy)
Symptoms & signs : fever, urticaria, polyarthralgia, lymphadenitis
Pathogenesis : T_h2 polarization
• type IV hypersensitivities

Pichler subclassification of type IV hypersensitivity reactions according to the pattern of cytokines involved and the effector cell recruited^ref:
• IV-a for a T_h1 cytokine pattern (IFN-g) and monocyte–macrophage activation
• IV-b for T_h2 cytokine pattern (IL-5) and eosinophil activation
• IV-c for activation of cytotoxic CD4⁺ and CD8⁺ cells
• IV-d where production of IL-8 and activation of neutrophils are predominant
• allergic contact dermatitis (ACD) / contact sensitivity (CS) / contact hypersensitivity (CHS)

Aetiology :
• chemicals (including occupation dermatitis / industrial dermatosis)
• metals
• mercury (Hg)
• nickel (Ni) sulfate in metal jewelry (necklace or bracelet), clothing snaps, zippers and metal-plated objects (coins, ...)
• cobalt (Co)
• hexavalent chromium plating on a cellular phone => erythema and papules on the hemilateral auricle or in the preauricular region.
• potassium dichromate, a tanning agent found in leather shoes and clothing
• drugs :
• penicillin
• ampicillin
• spiramycin
• neomycin sulfate in antibiotic skin ointments
• quinoform in topical antisepticals
• morphine
• propacetamol
• GR agonists
• dyes
• p-phenylendiamine in hair and cloth dyes
• azo-dyes
• ethylene
• diisocyanates
• methylenebisphenyl-4,4-diisocyanate (MDI)
• hexamethylene-diisocyanate (HDI)
• preservatives in solutions for topical use (parfums, ...)
• thimerosal in ophthalmic solutions
• formaldehyde
• chloramine T
• piperazine
• persulfate salts
• a-methyldopa
• triethylene
• disinfectants
• glutaraldehyde
• dodecyldimethylammonium
• ethylendiamine
• paraben
• wool alcohols
• cholesterol
• rubber accelerators : chemical additives used for vulcanization of synthetic and natural rubber latex (NRL) in gloves and "rubberized" clothing (common in health care professionals)
• thiuram-mix
• mercapto-mix
• carba-mix
• PPD-mix
Web resources :
• Allergy to Latex Education & Resource Team (ALERT)
• Cleveland Clinic Foundation : perioperative management of the latex-allergic patient
• Latex allergies
• Latex allergy by Daniel Suez, MD
• Latex allergy by Dr. Andrew Moore
• Latex allergy links
• Natural Rubber Latex (NRL) allergy discussion online
• dinitrophenyl (DNP), recognized by the monoclonal IgE SPE7
• trinitrophenyl (TNP)
• 2,4,6-trinitrobenzene sulphonic acid (TNBS)
• 2,4-dinitrochlorobenzene (DNCB)
• 2,4-dinitrofluorobenzene (DNFB)
• oleoresins in a type of marking fluid, bhilawanol oil, cause dhobie mark itch in laundry workers (dhobies) in India
• urushiol is an oleoresin contained in the leaves of Anacardiaceae family members (Quercus spp. (poison oak), poison ivy plants Toxicodendron radicans (a.k.a. eastern poison ivy, Rhus toxicodendron or Rhus radicans), Toxicodendron rydbergii, Rhus diversiloba, Rhus vernix, Anacarolium spp., Gluta spp., Mangifera spp., and Semecarpus spp.). The major and most active catechol in urushiol is pentadecylcatechol (PDC).


If urushiol is washed off the skin within an hour or so, the reaction can be largely prevented. However, if left on the skin, some diffuses through the skin, where it is metabolized to quinone derivatives. These form covalent complexes with skin proteins such as keratin. These complexes appear foreign to the immune system, which therefore attacks them. Lesion appears as a pattern of tiny lines or streaks in places where plant leaves have brushed against the skin (Rhus dermatitis / dermatitis venenata).
• poison ivy extract : an extract of the fresh leaves of Toxicodendron radicans used in desensitization for prevention of rhus dermatitis due to poison ivy.
• alum precipitated poison ivy extract : a repository form of a pyridine extract of poison ivy, Rhus radicans, used to counteract rhus dermatitis due to poison ivy.
• poison oak extract : an extract of the fresh leaves of Rhus diversiloba used for desensitization in prevention of rhus dermatitis due to poison oak.
Web resources :
• Poison Ivy Immunology
• Poison Ivy, Western Poison Oak, Poison Sumac by Gerald A. Mulligan
• Poison Ivy and Poison Oak Products at Wayne State University
• Poison ivy, sumac, and oak by the American Academy of Dermatology
• 4-tertiary-butylcatechol is an industrial chemical
• garlic, including the hematogenic variant^ref
• biologicals
• viruses
• mumps virus antigen
• bacteria
• tuberculin / tuberculoprotein / purified protein derivative (PPD)
• johnin
• lepromin
• diphteria toxin and toxoid
• Proteus mirabilis Ags
• streptokinase/streptodornase (SK/SD) (Varidase^®) used for the topical treatment of purulent and suppurating wounds/ulcers
• streptokinase (SK)
• staphylococcal toxoid
• tetanus toxoid (TT)
• brucellin INRA / brucellergen
• typhoid-paratyphoid
• Fungi
• candidin / oidiomycin (OID) (Candin^®). It is diluted 1:10 or 1:100 with sterile water. Administration is at a 0.1 mL volume injected intradermally into the volar surface of the forearm.
• trichophytin (Dermatophytin O^®)
• coccidioidin or spherulin
• histoplasmin
• blastomycin
• Protozoa
• leishmanin
• CCB (a polyvalent microbial vaccine from the Pasteur Institute)
• human erythrocyte-derived Thomsen-Friedenreich (T) antigen
• T cell mitogens
• Jarisch-Herxheimer reaction (JHR)

Aetiology : antibiotics increase the bioavailability of endotoxin from
• Gram-negative bacteria :
• Brucella melitensis
• Salmonella typhi
• Treponema pallidum subsp. pallidum
• Borrelia burgdorferi sensu latu
• Borrelia recurrentis
• Leptospira interrogans
• Coxiella burnetii
• Gram-positive bacteria :
• Tropheryma whipplei
• Metazoa
• Trichinella spp.
• Hymenolepis nana
• Enterobius vermicularis
• Trichuris trichiura
Pathogenesis : liberation of endotoxin-like substances or of antigens from the killed or dying microorganisms => increase in serum levels of TNF-a, IL-6 and CXCL8 / IL-8.
Symptoms & signs : acute fever, chills, headache, myalgias, rigors, systemic arterial hypotension and exacerbation of cutaneous lesions
Prognosis : transient, short-term
Prevention : anti-TNF-a mAbs
• photoallergic contact dermatitis : the cutaneous manifestations of photoallergy, consisting of a papulovesicular, eczematous, or exudative dermatitis, and occurring chiefly on the light-exposed areas of the skin.
• hypersensitivity pneumonitis(also type III hypersensitivity) : a respiratory hypersensitivity reaction to repeated inspiration of organic particles 0.5-5 mm in diameter, usually in an occupational setting, with onset a few hours after exposure to the allergen
• inorganic
• chemical worker lung : isocyanates as reagent for polyurethane, paint, foam or laquer synthesis
• anhydrides
• phthalic anhydride
• epoxy resin lung : in hot epoxy resin
• meat wrapper's lung : in meat wrappers or labels
• tetrachlorphthalic anhydride
• hexahydrophthalic anhydride
• trimellitic anhydride
• himic anhydride
• vineyard sprayer's lung : copper sulfate
• organic :
• bagassosis : mouldy bagasse (pressed sugar cane)
• thermophilic actinomycetes
• Saccharopolyspora rectivirgula
• Saccharomonospora viridis (a.k.a. Thermoactinomyces viridis)
• Thermoactinomyces sacchari
• Thermoactinomyces candidus (a.k.a. Thermoactinomyces vulgaris)
• Aspergillus fumigatus
• bird breeder's or pigeon breeder's lung : pigeons, parrot (Psittacidae), chicken (Gallus gallus) : proteins (IgA)  from stools or feathers
• duck fever : duck proteins in duck (Anas spp.) feathers
• turkey handler's disease : turkey proteins in turkey (Meleagris gallopavo) products
• hypersensitivity pneumonia due to Cephalosporium spp. in cellars contaminated from drains
• cheese handler's (or washer's) disease or lung : Penicillium casei on moldy cheese casings
• coffee worker lung : molds in coffee (Coffea spp.) dusts
• fertilizer lung : Aspergillus spp.
• detergent worker lung : Bacillus subtilis enzymes (subtilysin)
• familial hypersensitivity pneumonia : Bacillus subtilis on wood walls
• farmer's, harvester's or thresher's lung from Aspergillus spp.Micropolyspora faeni, Thermoactinomyces candidus (a.k.a. Thermoactinomyces vulgaris) and other actinomycetes termophilic actinomycetes which live on grain, straw or hay
• grain handler's lung : miscellaneous fungi in moldy grain
• fish workers lung : fish meal dust
• furrier lung : animal dandruff
• boiling bath lung : Cladosporium spp. on cellings
• hot tub lung
• humidifier lung : Amebae, Cephalosporium spp., Penicillium spp., Thermoactinomyces and other actinomycetes Aureobasidium pullulans, others in contaminated water of air conditioners, humidifiers, or dehumidifiers
• Japanese Summer house hypersensitivity pneumonia : Trichosporon cutaneum in house dust from bird stools.
• laboratory technician hypersensitivity pneumonia : male Rattus norvegicus urine
• lycoperdonosis : Lycoperdon spp. spores
• malt worker's lung : Aspergillus fumigatus and Aspergillus clavatus on moldy barley
• maple bark stripper's disease : a type of hypersensitivity pneumonitis affecting logging and sawmill workers, caused by inhalation of the spores of the mold Coniosporium corticale (a.k.a. Cryptostroma corticale), which grows under the bark of maple logs
• miller's lung : Sitophilus granarius (a.k.a. granary weevil) in infesed wheat flour
• mushroom grower lung : thermophilic actinomycetes, others
• Paulis hypersensitivity pneumonia : Paulis reagent
• heterologous hypophysis extracts
• potato siever lung : thermophilic actinomycetes, Aspergillusspp. on mouldy hay around potatoes
• sauna lung : Aureobasidium spp., others in contaminated water
• sequoiosis : Aureobasidium spp., Graphium spp. in moldy sawdust
• hypersensitivity pneumonia due to Streptomyces albus in contaminated manure
• suberosis : Penicillium spp. on moldy cork dust
• bath water lung : ? in contaminated water
• straw-roof disease : Saccharomonospora viridis (a.k.a. Thermoactinomyces viridis) on dried plants and leaves
• tobacco worker lung : Aspergillus spp. 
• viticulturist lung : Botrytis cinereaon grapes
• wood-painter disease : Rhizopus spp., Mucor spp.
• wood trimmer's disease : coaks and maple trees (Acer spp.)
• wood pulp worker's lung :  wood dusts (oaks, maple trees (Acer spp.), pine, and mahogany (Swietenia spp.)), Alternaria spp.
• Lyophyllumaggregatum
Symptoms & signs : fever, fatigue, chills, unproductive cough, tachycardia, and tachypnea
Laboratory examinations : BAL is diagnostic only when combined with symptoms & signs, radiology and RFTs ; in the chronic form there is interstitial fibrosis with collagenous thickening of the alveolar septa
• reactive erythemas / serum sickness-like reactions
• erythema nodosum (EN) : a type of panniculitis occurring usually as a hypersensitivity reaction to multiple provoking agents
• erythema nodosum migrans : a variant of erythema nodosum in which the lesions are asymmetrical, often unilateral, usually less acute and less numerous than those in the classic disorder, and characterized by the coalescence and clearing of older central nodules and formation of new lesions nearby, which gives the appearance of migration. Subacute nodular migratory panniculitis may be the same variant
Epidemiology : it most often affects young women
Aetiology :
• infections
• Bacteria
• Streptococcus spp.
• Mycobacterium tuberculosis
• Mycobacterium leprae (erythema nodosum leprosum (ENL))
• Brucella melitensis
• Mycoplasma spp.
• Rickettsia spp.
• Chlamydia spp.
• viruses
• Fungi
• Coccidioides immitis
• Ajellomyces capsulatus
• drugs
• sulfonamides
• oral contraceptives
• autoimmune diseases
• sarcoidosis
• inflammatory bowel diseases
• idiopathic
Pathogenesis => symptoms & signs : panniculitis => crops of transient, erythematous, painful, nonulcerating nodules that are usually tender, multiple, and bilateral, and most commonly located on the shins (and sometimes even upper limbs); the lesions involute slowly, leaving bruiselike patches without scarring. The acute disease is often associated with mild constitutional symptoms, including fever, malaise, and arthralgias. A chronic variant sometimes occurs without any serious associated systemic disease
Prognosis : self-limiting 6-8 weeks after removal of aetiological factors
Web resources : Erythema Nodosum Research and support group by Rebecca Strecker
• erythema multiforme : sudden onset of an erythematous macular, bullous, papular, nodose, or vesicular eruption, the characteristic lesion being the iris, bull's eye, or target lesion / erythema iris, which consists of a central papule with 2 or more concentric rings.
• gyrate erythema / erythema gyratum / figurate erythema / erythema figuratum : erythema multiforme characterized by the development of gyrate, figurate, circinate, annular, arcuate, polycyclic, serpiginous, or reticulate lesions that tend to migrate and spread peripherally with central clearing. There are 3 basic types
• erythema chronicum migrans (ECM) / erythema migrans : a deep form of gyrate erythema caused by the spirochete Borrelia burgdorferi, with the tick Ixodes ricinus as the vector, characterized by the development at the site of a tick bite of a red papule that expands slowly, producing an annular lesion with central clearing, and often associated with systemic symptoms, including chills, fever, headache, malaise, nausea and vomiting, lumbago, and stiff neck.
• Darier's erythema annulare centrifugum (EAC) / erythema figuratum perstans / erythema gyratum perstans

: an often mild but chronic and recurrent form of gyrate erythema characterized by the occurrence of crops of annular wheal-like lesions with edematous, sometimes vesicular, borders and commonly a yellowish central region that exhibits a fine branny scaling, which may coalesce.
• erythema giratum repens : a superficial form of gyrate erythema almost always associated with internal malignant cancers, which is characterized by the presence of migratory wavy bands of slightly elevated erythema with a scaly collarette over the entire body, and sometimes accompanied by pruritus.
• erythema marginatum (rheumaticum) / erythema annulare (rheumaticum) / erythema circinatum (rheumaticum) : a superficial, often asymptomatic, form of gyrate erythema associated with some cases of rheumatic fever, which is characterized by the presence on the trunk and extensor surfaces of the proximal limbs of a transient eruption of flat to slightly indurated, nonscaling, multiple pink-reddish maculae or papulae after hot shower
• erythema multiforme minus / Hebra's disease : a mild self-limited mucocutaneous form of erythema multiforme that may have a prodrome of fever, cough, and acute pharyngitis. In addition to the characteristic iris lesions, erythematous macules and papules, purpura, and occasional vesiculobullous lesions may be present on feet, which are usually asymptomatic, but may burn or itch slightly

Aetiology :
• infections :
• HHV-1 / HSV-1
• HHV-2 / HSV-2
• orf virus
• Mycoplasma spp.
• Coccidioides immitis
• drugs
• margarine disease : name given to an outbreak of erythema exudativum multiforme in Germany and The Netherlands in 1958 in children that was due to a byproduct of a new surfactant which had been added to a margarine brand as anti-spattering (emulsifier) agent, i.e. a surfactant that keeps the water droplets finely dispersed during frying. Sensitizing agents are electrophiles that react with the nucleophilic groups of proteins, creating unnatural protein derivatives which the body than detects as foreign. The margarine surfactant contained an appreciable amount of an unreacted intermediate, a maleic anhydride derivative, which could be ring-openede in the body by amino or thiol groups.
• pregnancy
• radiotherapy
• idiopathic (50%)
Pathogenesis => symptoms & signs : symmetrical, small dermal-epidermal vesicles on dark purpureal maculae or atypical target all over the body.
• erythema multiforme majus / Stevens-Johnson syndrome (SJS) / ectodermosis erosiva pluriorificialis

Aetiology :
• infections
• Mycoplasma pneumoniae
• Coccidioides immitis
• allopurinol
• barbiturates
• codeine
• thiazide diuretics
• phenolphthalein
• antimalarial drugs
• iodides
• COX inhibitors
• phenylbutazone
• piroxicam
• salicylates
• celecoxib
• antimicrobial drugs
• antifungal drugs
• imidazoles
• antibacterial drugs
• penicillins
• aminopenicillins
• cephalosporins
• tetracyclines
• nalidixic acid
• sulfones
• sulfonamides (including cotrimoxazole)
• sulfamethoxazole or its nitroso metabolite, but not its hydroxylamine metabolite
• antiviral drugs
• NNRTI
• abacavir
• amprenavir
• calcium channel blockers (CCB)
• valproic acid
• ethosuximide
• Na⁺ channel blockers
• carbamazepine
• lamotrigine
• phenytoin
• tocainide
• chlormezanone
• thiacetazone
• amifostine
Pathogenesis : widespread apoptosis of keratinocytes expressing drug-derived antigens at their surfaces, resulting from perforin/granzyme-mediated cytotoxicity (without implication of Fas or TRAIL) by CD8⁺56⁺ T lymphocytes, HLA-DR⁺, CLA⁺
Symptoms & signs :
• flulike prodrome : throatache, malaise, fever (10-30%) => vasculitis => erythema multiforme, rare rapid confluence areas, skin detaching on < 10% of body surface area
• mucosal erosions in > 2 sites
• oronasal  mucous membrane : gray or white pseudomembrane
• lips : hemorrhagic crusts
• oesophageal boils
• URT => asphyxiaanogenital mucous membrane : gray or white pseudomembrane
• ocular lesions : conjunctivitis, iritis, uveitis, corneal vesicles, erosions, and perforation, which may result in corneal opacities and blindness
• pulmonary
• gastrointestinal
• arthritis
• nephritis
• CNS abnormalities
• myocarditis sometimes fatal
Therapy : GR agonists in the phase of progression (withdraw them as soon as possible as they also greatly enhance the risk of infection, the complication which most frequently leads to a fatal outcome), add antibacterials for prophylaxis, supportive treatment and monitoring of vital functions
Prognosis : recovery is usually slow, depending on the extent and severity and the presence of complications, and may take 3-6 weeks. Skin lesions heal without scars as a rule, but scarring of mucosal sites is a frequent late complication, potentially leading to blindness, obliteration of the fornices and anogenital strictures.
Web resources : Stevens-Johnson Syndrome Foundation
‡
• toxic epidermal necrolysis (TEN) / toxic bullous epidermolysis / Lyell syndrome : an exfoliative dermatitis / scalded skin syndrome
URT febrile illnesses caused by various viruses, mycoplasma, chlamydia infections, and/or inflammatory diseases are usually observed a few days to a few (several) weeks before the onset of Reye's syndrome, Stevens-Johnson syndrome, autoimmune hepatitis (hepatotropic virus infections), or hepatotoxicity associated with therapeutic administration of acetaminophen in persons with varying degrees of deficits of important enzymatic activity. Activation of systemic host defense mechanisms by inflammatory component(s) results in depression of various induced and constitutive isoforms of cytochrome P-450 mixed-function oxidase system superfamily enzymes in the liver and most other tissues of the body. Because several cytochrome P-450 enzymes activities important for biotransformation of many endogenous and exogenous substances show considerable variability between individuals, in some genetically predisposed persons, even the administration of therapeutic doses of a drug may result in serious clinical mishaps, if an important concomitant risk factor (eg, acute viral infection) is involved. Several inflammatory cytokines, such as ILs, TGF-b₁, HGF, and lymphotoxin, downregulate gene expression of major cytochrome P-450 enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity observed with a given cytokine varying for each P-450 studied, thus eventually leading to metabolite-mediated adverse drug reactions and immunometallic diseases which sometimes result in tissue injury beyond the site(s) where metabolic bioactivation takes place. On the other hand, it must be emphasized that inhibition of metabolism of several drugs, as well as influence on the concentration and/or ratio of various cytokines in inflamed tissues, may exert beneficial effects in patients with different diseases, thus opening new therapeutic possibilities. Clinically relevant interactions may be exemplified by the effects of some fluoroquinolone antibiotics, such as pefloxacin and ciprofloxacin, which probably have a steroid-sparing effect in some patients with frequently relapsing nephrotic syndrome, and an increased bioavailability of several drugs following concomitant intake with freshly pressed grapefruit juice, eventually caused by inhibition of their metabolism, mediated mainly by CYP3A and specifically inhibited by naturally occurring flavonoids.
• infectious agents
• Bacteria
• tubercle => tuberculoma due to Mycobacterium bovis, Mycobacterium tuberculosis
• leproma due to Mycobacterium leprae
• syphiloma and gumma due to Treponema pallidum subsp. pallidum
• mycetoma due to Fungi or Streptomyces spp. or Nocardia spp.
• Brucella melitensis
• lymphogranuloma venereum due to Chlamydia trachomatis
• rhinoscleroma due to Klebsiella pneumoniae subsp rhinoscleromatis
• granuloma inguinale due to Klebsiella granulomatis
• granulomas due to :
• Actinomyces spp.
• Bartonella spp.
• Burkholderia mallei
• Corynebacterium pseudotuberculosis
• Treponema pallidum subsp. pertenue
• Protozoa
• trypanoma due to Trypanosoma brucei
• chagoma due to Trypanosoma cruzi
• granulomas due to :
• Leishmania donovani
• Naegleria fowleri
• Fungi => mycetomas
• aspergilloma due to Aspergillus spp.
• coccidioidoma due to Coccidioides immitis
• histoplasmoma due to Ajellomyces capsulatus
• cryptococcoma or toruloma due to Filobasidiella neoformans var. neoformans
• Eumetazoa => granulomas due to :
• Schistosoma spp.
• Anisakidae spp.
• Baylisascaris procionis
• Toxocara canis
• Toxocara cati
Pathogenesis : T_h1 polarization
Symptoms & signs : erythema and intracellular edema in epidermal layers (spongiosis) => blistering and severe itching. If chronic => dermatofibrosis, with pigment changes and areas of hair loss, persisting for many years.
Diagnosis by patch test : small pieces of gauze or filter paper impregnated with sussmall amounts of specific pected allergens are applied to the skin of your back, and then covered with tape, for fixed time periods. After 48 hours, the doctor removes the tape and examines the underlying skin for signs of an allergic reaction; swelling or redness constitutes a positive reaction. A second reading is done after 3-7 days.
• AL test : a type of patch test in which the materials being tested are applied to cellulose disks arrayed on polyethylene-coated aluminum paper, which is affixed to the skin for several days
• Finn chamber test : a type of patch test in which the materials being tested are held in shallow aluminum cups (Finn chambers) that are taped against the skin, usually for several days.
• thin layer rapid use epicutaneous (TRUE) test : a ready-to-use method for patch testing, consisting of a desiccated mixture of allergen and hydrophilic gel printed on a mylar backing; after application the gel absorbs water from the skin and releases allergen.
• complications : excited skin syndrome / angry back : nonspecific cutaneous hyperirritability of the back, sometimes occurring when multiple positive reactions are elicited in patch tests screening a battery of substances
Therapy : fluorurated glucocorticoids, MnSO₄ solution to reduce the itching, nonirritating moisturizer to help restore the normal texture of the skin (ointment or cream that contains few potential allergens : petroleum jelly, Vanicream, Cetaphil, Eucerin, oatmeal baths (Aveeno))
Prognosis : clear up within 1-2 weeks, as long as you stop exposing your skin
Web resources :
• List of substances causing allergic contact dermatitis
• Contact dermatitis home page by A.P.Truett at Vanderbilt University
• Camper with a rash by Lewis Nelson at Yale University School of Medicine

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