A review on Respiratory allergy caused by insects
Abstract
BacAllergy and Insect:
Allergens are usually proteins or glycoprotein or chemicallycomplex substances with low molecular weight. Their molecularcomplexity, concentration, solubility and stability in body fluidswere other important determinants of allergenic potential 1. Thecommon allergens include pollen, fungal spores, house dust mite,and house dust, animal dander, insect emanations and detritus,drugs, foods, etc. Out of these, the allergenic significance of a largenumber of pollen grains, fungal spores, animal danders, house dustand house dust mite has been extensively studied all over theworld including India and was very well established 2-9. The roleof insects as sources of inhalant allergens insects was also wellstudied and suggested insects were one of the most importantsources of aeroallergens.Insects, an important class of the phylum Arthropoda, werecharacterized by an exoskeleton, a body showing segmentation andbilateral symmetry and jointed appendages. The numbers ofinsects' species were more as compared to any other group ofanimals. An insect mainly highlights the world most diverse groupand numerous classes of the animal kingdom and includes anumber of species i.e. praying mantis, dragonflies, grasshoppers,true bugs, flies, fleas, bees, wasps, ants, lice, butterflies, moths, andbeetles. The number of species of insects was estimated to bebetween 6 to 10 million with more than a million species alreadydiscovered. They assume the role among more than half of allliving organisms that were known presently and potentially serveas more than 90% of the different forms of life on Earth. Hence,contacts of the human with insects were inescapable. Human exposure to biting or stinging insects or to their remains may rangefrom conditions in which they were barely noticeable to severe lifethreateningconditions. From studies conducted by Terry Erwin ofthe Smithsonian Institution's Department of Entomology in LatinAmerican Forest Canopies, the number of living species of insectshas been estimated to be around 30 million 10. Insects fall under33 orders, which were further divided, into 839 families 11. Of allthe insects, moths, butterflies, bees, wasps, hornets, yellow jackets,flies and mosquitoes constitute about 40 percent, the beetlesanother 40 percent and the rest about 20 percent 12. These insectscan be broadly be classified as stinging insects, biting insects andnon-stinging and non-biting insects 13. All insect matter likewings, scales, saliva, dried fecal matter, and venom can causeallergic diseases such as rhinitis, conjunctivitis, asthma, urticariaand gastric disorders 14,15 . Depending on the route ofsensitization, the insect allergens have been recognized as aninhalant, ingestant and injectant allergens 16.
Insect’s leads to a number of allergies that in turn results in pain,itching and appearance of redness and swelling at the bite/sting orsurrounding affected areas. It has been reported that peopleallergic to stinging venom may possess certain serious reactionnamely anaphylaxis 17,18 . It has been reported that from the lastdecade the number of patients with respect to insect allergy hasincreased. However, mortalities have been known to reduce mainlydue to improved diagnosis and upgraded treatment procedures.The socio-economic burdens linked with insect-related allergieswere still unknown. Insect prone allergies were also known asHymenoptera Venom Allergy (HVA). The HVA allergies have beenknown to cause large local reaction (LLR) or systemic allergicresponses. The induced allergic responses affect the local area andresult in the depth of more than 10cm within 24 hours at the stingsite. Hymenoptera mainly belongs to the sub-order Aculeate andconstitutes several super-families namely Apoidea, Vespidae, andFormicidae [18]. The common insect’s varieties in these familiesinclude: (1) Yellow Jackets; (2) Honeybees; (3) Paper wasps; (4)Hornets. The allergens which mainly initiates allergic response viahoneybee sting were phospholipase A2 (Api m 1) andhyaluronidase (Api m 2). Allergens in yellow jacket’s venominclude (1) Phospholipase A1 (Ves v 1); (2) Hyaluronidase (Ves v2); (3) Antigen 5 (Ves v 5). Allergens particularly found in Fire antsinclude: (1) Sol r 2 (A Phospholipases); (2) Sol i 2; (3) Sol i 3; (4) Solgem 2.
Insect bite and sting:
Insect breaks or punctures in the skin via bite and/or sting. Theconditions became complicated when insect introduce their saliva,venom or excretory products into the skin through puncture. Thespecific components present in these injected substances wereprone to give rise to an allergic reaction. These allergic reactions, inturn, result in the appearance of skin lesions that may vary from atypical small itching wheal or slightly elevated area of the skin tofurther large painful areas of inflamed skin covered thoroughly byvesicles and crusted lesions. The member of flying insects namelyflies, gnats and mosquitoes mainly attack the exposed parts of thebody. Each bite results in a single itchy wheal that subsequentlydiminishes within hours. Crawling insects may attack any part ofthe body including the covered areas of the body and generatescharacteristic skin diseases particular to each insect variant. Scabiesor sarcoptic itch invades the skin and leads to inflammationparticularly by the itch mite, Sarcoptes scabiei. The female mites attack the skin and burrows beneath thesuperficial layer of the skin to lay its eggs in a tunnel visible as adark wavy line. This lesion initially becomes intensely itchy. Aftera couple of days to few months, the scratching further developsinto secondary skin lesions with papules (solid elevations),pustules and crusted skin areas. The itchiness that appears wascaused due to the accumulation of fecal deposits by the mite in theburrow region. Scabies is commonly observed between the fingers,other persistent locations besides fingers being the natural folds ofthe skin and pressure areas.
The symptoms of a severe systemic allergic reaction to an insectsting include: (1) A sudden feeling of weakness (caused by a dropin blood pressure); (2) Dizziness; (3) A sense that something terribleis happening; (4) A rapid pulse; (5) Swelling of the airways andthroat, making it difficult to breathe; (6) Severe asthma; (7) Itchingand swelling away from the site of the sting; (8) Stomach crampsand/or a feeling of sickness Pediculosis is the skin disorder caused bloodsucking lice. Thesebloodsucking lice belong to various species and infect the scalp,groin, and body. The lice invade near or onto the skin and attachtheir eggs to the hair or clothing of the host on which theyfrequently feed. As a result, a small itchy red spot appears and mayfurther become infected after repeated scratching. Chiggers i.e. thelarvae of certain mites’ were an inhabitant on humans and suck theblood. The bite of chiggers produces a wheal on the skin withintense itchiness. The itchiness has been known to occur as a resultof the digestive juices of the chiggers being injected while feedingblood. Other bloodsucking insects that in habitat humanswere fleas, bedbugs and ticks, that originally lives in the ground,bedding, walls, and furniture and temporarily act on humans asprimary hosts. The most commonly observed lesions on humanswere of bedbug and fleas. Bedbug produces a burning whealsensation with the central punctured dot. The flea results in acluster of wheals and papules since fleas injectseveral adjacent spots in the course of feeding on the skin.Insect’s sting generated by the family of stinging insect resultspainful swelling of the skin and the severity of the lesion variesaccording to the site of the sting and the type of the insect. Avariety of species of bees and wasps belongs to the family ofstinging insect. They possess two poison glands. One gland isengaged in secreting toxin with formic acid as one the mostrecognized constituent. The other gland secretes an alkalineneurotoxin that acts independently. The secreted toxins wereindividually mild by nature, but when grouped and injectedtogether via stinger, the combination leads to strong irritatingproperties. In some cases, the bee or wasp sting causes a severeallergic reaction known as anaphylaxis. Other examples of stinginginsects were Hornets, some ants, centipedes, scorpions, andspiders. Some insects leave their sting in the wound. In such caseswhen multiple stings were being injected, it may give rise to severesystemic symptoms and in severe cases may lead to death. Thebites of some spiders were reported to be lethal, particularly inyoung age group children.
The Global Prevalence of Insect Allergy:
The prevalence of insect allergy worldwide is approx 1 to 7% 19with more ubiquity reported among the middle and old-agepopulation 20,21. The average pervasiveness was mainly to largelocal reaction of about 2.4% -24.6% among general population up to38% in beekeeper’s population. In US, the common inset derivedallergies were caused by Paper wasp, Yellow Jacket, Hornet andEuropean Hornet with the prevalence of 0.5- 3.3%. According toworld allergy organization, around 40 deaths per year in US werereported to be occurred as a result of insect allergy. The prevalencepercentages of insect-borne allergy were reported to be higher inUK as compared to US by 11.5% people being infected 22. Themost preferred allergy among the entire key allergy includes beewaspallergy with 2% prevalent in the population. Other than beewaspallergy, hornet imposed allergic reaction was reported in UKpopulation 23. Furthermore, in Australia, nearly 15-25% of thetotal populations were diagnosed with different insect allergies.The major cause of allergy being from ant stings mainly AustralianJack Jumper Ant 24. In Japan, more than half of the totalpopulations i.e. 61.5% were reported to be affected by insect allergyleading to high fatality rate 25. The increased percentages ofinsect prevalence were reported in the case of Africa with 28%.Among the common allergies, the most preferred allergic reactionswere known to be caused by black flies, which are responsible forthe transmission of onchocerciasis 26.
The estimated prevalence of subjects with experienced immediatesystemic reactions to insect stings varies from 1-7% of the totalpopulation. The insects that was responsible and accountable forthe sting related problem was found to vary by region. Thehoneybee is ubiquitous, yellow jackets (Vespula) were responsiblefor sting allergy problems across diverse temperate climates, paperwasps (Polistes) and hornets (Vespa) tend to be important at lowerlatitudes. Stinging ants were more restricted by distribution, withexception of the imported fire ant (Solenopsis invicta) and jackjumper ant (Myrmecia pilosula spp) that dominates clinical stingallergy in areas of South Eastern-South Central USA and SouthEastern Australia respectively. The species of Pachycondyla resultsin major public health problems in East Asia and the ArabianPeninsula region. Recently, anaphylaxis resulting from the bite ofthe paralysis tick, Ixodes holocyclus has been reported as anemerging problem on the east coast of Australia and has beenfound to be associated in many subjects with subsequentanaphylaxis to red meat. There have been many reports ofanaphylaxis to tick bites in Europe. It has been found that bitesresulting from Ixodes in Australia and Europe and Amblyomma andDermacentor spp in North America were important stimuli withrespect to sensitization to the carbohydrate allergen, galactosealpha-1,3 galactose. It has been also reported to be widespread innon- primate animals and also linked to allergic reactions to themonoclonal antibody cetuximab. Anaphylaxis related to bitinginsects like kissing bug (Triatoma), horseflies (Tabanus spp) andmosquitoes (Aedes, Culex and Anopheles) has been rarely reported.The estimated numbers of deaths resulting from the stinganaphylaxis were likely to vary widely regionally. It has beenreported to lie most likely in the range of 1-10 per 10 million perannum based on estimates in the USA and Australia.The prevalence of insect allergy in Indian sub-continent wasreported to be 30% i.e. one-third of Indians from the totalpopulation was suffering from insect allergies mainly due to hugediversity and lack of basic prevention strategies. The most commoninsect allergy prevalent in India is mainly due to honeybee stings.The common allergies prevalent across the major countries aroundthe globe were summarized in Table 1.
Diagnosis and Therapeutic review of insect allergy:
The diagnoses of insect sting were mainly judged through limitedswelling of the local area being stringed. However, mostly only inminority of cases, the swelling can prolong by 24-48 hours.Furthermore, only a small percentage of individuals developsystemic reaction beyond the area of sting leading to IgE mediatedreaction. Hence, diagnosis in case of insect allergy is crucial for thetreatment of individuals. Among the common diagnostic testsbeing used, skin test is the most common with 90-95% accuracy[17]. However, there is a need of specialist evidence regarding thediagnosis with sting because the availability of venom-specific IgEis difficult. Thus, in such case sensitivity test for different types ofinsects should be carried out. Consequently, another test that iscommon besides skin test in the diagnosis of the disease is themeasurement of Mast Cell Tryptase. The measurement should becarried out within 30- 38 hours of the sting bite in order to concludean allergic reaction 27. At last, another diagnostic tool that hasbeen particularly in use but not widely used is sting challengemostly applicable in clinical practice. In India, blood test and skintest were most commonly used to determine insect-specific allergicreactions.
In mild cases of insect allergy, anti-histamines were given with oralprednisolone. Further, H1 and H2 antihistamines were used toenhance the effect of diphenhydramine 28. However, in case ofsevere infection, venom immunotherapy was given as a treatmentprocedure. Epinephrine injections were also considered asmanagement for the allergy 29. Local reaction such as coldcompresses, elevation of the affected limb, anti-inflammatory, andoral corticosteroids can also be used 30. In India, Japan and UK,several medicinal plants have been used for the treatment of insectbite. They use the extract from the plant such as terpenoids,flavonoids, tannins, and cardiac-glycosides. These plants havetriple effect of anti-bacterial, anti-inflammatory and anti-viralreaction 31.
Insects sting allergy and Neuro problems:
The exposure of humans to insects or insect material may lead tothe allergy that can be natural, domestic, hobby-related andoccupational 32. Prior to 1960, a few scattered reports on asthmaor rhinitis due to exposure to insect allergens were available. Theseinsects include may fly, aphid, caddisfly, housefly beetles etc 33-36. Feinberg and coworkers (1956) carried out skin tests withinsect extracts on a large number of patients suffering from asthma,hay fever, atopic dermatitis, and conjunctivitis and reported thatmost of them showed a positive response, indicating that the dustof disintegrated insects might be an important cause of inhalantallergy [36]. After that, a number of studies with high incidence ofskin positivity to insect extracts were reported among patients ofbronchial asthma or allergic rhinitis 37-39.
A number of stinging insect’s allergic reactions in humans havebeen also reported. The most commonly studied includes waspsnamely hornets (Vespa), yellow jackets, European wasps (Vespula)and paper wasp (Polistinae); bees namely honey (Apis mellifera) andbumble bees (Bombus) and stinging ants such as fire ants(Solenopsis), jack jumper and bull ants (Myrmecia, and Pachycondyla)40. The basic sting reaction comprises of three types and thesymptoms were dependent on the site of sting. Stings in the mouthmay cause serious airway obstruction even in case of people whowere not hypersensitive to the venom. Systemic manifestationsmay include hypotension, broncho-constriction, respiratorydistress, syncope, laryngeal edema and death. The classified werebased on the severity of grade of insect sting (Table 2). The normalsting reaction where the area around the bite becomes red followedby itchiness and severe pain; a large local sting reaction withswelling areas greater than 5 cm and systemic reactions withsymptoms arising in areas other than the area of bite 41. In somecases, a large local reaction may occur with skin redness greaterthan 10 cm 42. It can last for about two days and known to beoccurred in about 10% of bitten cases 43. In case of some persons,excessive local swelling may develop that can be either immediatei.e. developing and peaking within 1-2 hours or can be delayeddeveloping after 24 to 48 hours of the sting and eventually resolveafter 3-10 days of biting. A small range of the population maydevelop systemic or generalized reactions extended beyond theneighboring areas. These were mostly immediate IgE-mediatedallergic reactions and mainly comprises of cutaneous, mucosal,respiratory, cardiovascular, gastrointestinal and neurologicalinvolvement (Table 3). Systemic reactions have been classified bythe four-stage system of Ulrich Mueller with a modification in thesystem of Harry Mueller described earlier.
Nowadays, Simon Brown described a new three-tier system (Table 2) describing the significance of features that increase theprobability of occurrence of hypoxia or hypotension. Recently,WAO has proposed a classification covering standard reports ofreactions to subcutaneous immunotherapy 44. Human exposuresto insects were often associated with most notable immediate risklike anaphylactic shock. Hypersensitivity arising as an outcome ofharmless insect saliva, venom, body parts, excretions or secretionsmay result systemic responses in case of some individuals.Diagnosis of the early phases of the systemic allergic reactionleading to an anaphylactic shock is of great importance in terms oftreating any patient suspected with insect exposure. Anaphylaxismay be fatal in the time duration of 10 minutes in severe cases. Therate of reoccurrence is around 40-60% in insect stings 45. In India,systematic detailed research on the significance of insects in theetiology of allergic respiratory disorders and their treatment byimmunotherapy was initiated in 1969 by Shivpuri and coworkers46. Shali and coworkers (1970) reported the presence of some sexspecificallergens and antigens in the WBE (Whole Body extract) ofmale and female cockroaches (Periplaneta americana) 47.
They gave evidence for the presence of sex-specific allergens in thecockroach. In 1971, Shivpuri and coworkers published the resultsof another detailed study on insect allergy 48. Subsequentextensive research conducted by Agarwal and co-workers in thefield insect allergy conclusively established that insects play animportant role as sources of inhalant allergens in the etiology ofallergic respiratory diseases 49-56. Chaudhry (1988) conducted asystematic and comprehensive study on the clinico-immunologicproperties of twelve insects and reported that all these insects play animportant role in type I allergic respiratory disorders 57. Theseinsects included cockroaches (Periplaneta americana and Blattellagermanica) male and female; housefly (Musca domestica); locust(Schistocerca gregaria) male and female; mosquitoes (Aedes aegypti,Anopheles stephensi and Culex quinquefasciatus) and moths (Heliothisarmigera and Spodoptera litura). It has been reported that venoms andsaliva of insects play an important role in the etiology of allergicrespiratory diseases. Venom hypersensitivity may not only bemediated by immunologic mechanisms (IgE-mediated or non-IgEmediatedvenom allergy) but also by non-immunologic mechanisms 58. Several major allergens usually glycoprotein have been identified in venoms of bees, vespids and ants 59. The structures and sequences of the majority of venom allergens have been determined and several have been expressed in recombinant form 60,61.
The insects belonging to Hymenoptera order comprises of wasps,bees and ants inject their venom via stinging. The venom injectedby distinct species has been found to differ in terms of biochemicaland immunological backgrounds, however; cross-reactivitybetween some species has been found 62. Wasp venom containsthrombogenic, vasoactive and inflammatory peptides; amines;enzymes; low molecular weight compounds i.e. serotonin,histamine, and acetylcholine. The occurrence of reactions as anoutcome of venom injection might be local, regional, systemicanaphylactic and delayed-type hypersensitivity 63. The venom ofinsect’s wasps, bees and ants induces acute IgE-mediated type I ortype III hypersensitivity reaction with the impeachment of immunecomplexes and complement activation. These reactions weremainly delayed and reported to occur within days to several weeksafter the inoculation of venom. Neurologic symptoms governingHymenoptera stings were mainly uncommon, but several caseshave been reported globally with both central and peripheralnervous system involvement. These can be cranial neuropathies,acute inflammatory polyradiculoneuropathy, stroke, encephalitisand myasthenia 64. There have been reports about wasp sting–induced allergic encephalitis worldwide with 2 from Russia and 1from India 65. In these reports headache and seizures andresponse to steroids were observed 66. Although hypothalamichamartoma, gelastic seizures associated with different cortical focii.e. frontal, temporal, and parietal were also reported 67. It hasbeen found that in case of stings incorporating by a large swarm ofstinging insects may lead to mass envenomation and the patientmust be treated aggressively and observed within 12 to 24 hoursfor the development of coagulopathy, renal and neurologicaldamage.
Clinical studies with different insects:
Moths and Butterflies:
The order Lepidoptera comprises of moths and butterflies and theirlarvae i.e. caterpillars. There have been an estimated 125,000 to150,000 different species of moths and butterflies in this order.However, few were capable of inducing adverse reactions inhumans. Caterpillars were mainly responsible for the majority ofadverse reactions occurring among humans. Adult moths andbutterflies do not appear to cause any adverse reactions in humans.The Lepidoptera order possesses two sub-orders i.e. OrderRhopalocera comprises of adult specimens that fly during daytimeand were commonly known as butterflies and Order Heterocerawith nocturnal activities and were called as moths. In a studycomprising lepidopterans (butterflies and moths) derived skinlesions found that lesions were found to be appear by twomechanisms. First, through contact with irritating hairs or setae ofsome caterpillars and secondly by the action of body setae of adultmoths, that were considered rare 68,69. Their phases ofdevelopment include egg; larva or caterpillar, pupa or chrysalisand an adult phase called imago and represent a complete orholometabolic evolution 70,71 . Generally, the pathophysiologicalcomplications related to toxic moths and caterpillar exposures wereclassified into several clinical syndromes. These include erucism i.e.disorder occurs as a result of reactions due to caterpillars;lepidopterism comprises of cutaneous and systemic signs;pararamose with severe arthralgia and arthritis due to spp. ofPremolis caterpillars; lonomism due to contact with Lonomiacaterpillers; dendrolomiasis due to exposure to Dendrolimuscaterpillars and ophthalmia nodosa with ocular involvement 72-74(Table 4). The caterpillar-induced bleeding syndrome is aunique disorder belonging to the Lonomia genus, a type of mothnative to South America. Around 688 cases of caterpillarenvenomation were reported in the state of Rio Grande do Sul inBrazil during periods of 5 years 75. These bleeding syndromeswere known to cause by two species belongingto Lonomia caterpillars 76. They were L. oblique, native to southernBrazil and L. achelous commonly found in Venezuela and northernBrazil. Both caterpillars were reported to induce a consumptivecoagulopathy and bleeding syndrome in a similar way. Althoughthe pathophysiologic processes behind the occurrence of thebleeding syndrome were not fully known, the mechanism viawhich this occurs was reported to be slightly dependent on thecausal species. Caterpillar-induced bleeding syndromes werecharacterized by initial symptom like mild fever, local burningpain, headache, nausea, and vomiting 77. As clotting factors wereconsumed via venom-induced activation of the coagulation system,within 1 hour to around 10 days several bleeding complicationsarise. These bleeding manifestations include mucosal hemorrhages,hematuria, and ecchymosis after envenomation. In case ofLonomia envenomation alveolar hemorrhage, acute renal failureand intracranial hemorrhage occur 78.
When poisoning was linked with caterpillars of the species L.obliqua, the signs and symptoms after bristles contact includessevere pain with burning sensation, redness and swelling at the siteof contact site, general malaise, vomiting, shortness of breath,bruising, mucous membranes bleeding, epistaxis, melena,hematuria, anuria, hypotension, headache, arthralgia, myalgia,back pain, weakness and fever 79,80.A number of cases werereported with allergy to these two insects 81.
Parlato (1932) was the first to report respiratory allergy caused bymoths and butterflies 82. He reported that scales and hair of theseinsects (Lepidoptera) were commonly found in the air. Studiesconducted by Kino and Oshima also implicated these insects as thepossible cause of respiratory allergy 83-85. They found that morethan half of the randomly selected asthmatic population showednot only positive skin tests and RAST but also positive bronchialprovocation reactions to these outdoor insects. They did not findany cross-reactivity between house dust mite and moth allergens.Wynn and coworkers (1988) immunochemically measured the airborn concentration of Lepidoptera allergen and concluded thatmoth might be a seasonal allergen 86. Araujo and coworker(2014) reported high frequency of sensitization to Bombyx mori(Moth) in a selected population of patients with respiratory allergicdiseases 87. Wills and co-workers (2016) reported that allergicdiseases are a disease caused by the scales and toxic fluids of adultmoths and butterflies 88.
Midges
Midges were tiny flying insects with 2-3 mm length wingspan.Around the world, 20,000 species of midges were identified and themajority of them were non-biting midges. A female midge has beenonly known to bite, as they need blood to feed their eggs. Malemidges only invade plants and suck plant nectar. Culicoides isa genus of biting midges belonging to the ceratopogonidae family.There were over 1000 species in this genus 89 divided into manysub-genera. Several species were known to act as vectors of variousdiseases and parasites eventually affecting animals.Culicoides biting midges (Diptera: Ceratopogonidae) are among thesmallest blood-sucking flies 90. The Culicoides biting midges inpublic health were reported to biologically transmit Oropouche virus(OROV), the etiological agent of the febrile illness Oropouche feveramong human beings 91. The most commonly observedsymptoms of Oropouche fever were mainly headache in most ofthe cases, followed by generalized arthralgia, anorexia and insevere cases meningitis, the incidence of which were presentlyunknown in the majority of epidemics 92. The distribution andincidence of endemic OROV were currently under review and werefound to be somewhat linked to the recent discovery in Peru ofIquitos virus, which possesses similar clinical manifestations butthe mode of transmission has been yet to be investigated in detail93. In addition to OROV, Culicoides also play an important butlimited and poorly defined role in the transmission of many otherzoonotic arboviruses, which were of paramount importance. Otherhuman pathogenic arboviruses have also been detected in fieldcaughtadult female Culicoides and oral susceptibility has beenfound for Rift Valley fever virus (RVFV), following initial detectionin field populations.
The two cases of Chironomus thummi allergy were reported by Baurand co-workers (1980) 94. They reported that 20% of sera from642 chironomids exposed subjects developed immediate-typehypersensitivity and had significantly raised levels of specific IgEantibodies. Later several other reports were published from variousparts of the world suggesting that chironomid particles were one ofthe important inhalant allergens causing asthma 95. Contact withthese insects takes place where there are abundant water i.e.Japanese rice fields 96, hill region of Sudan 97 and lake areas inWisconsin, U.S.A. 98. In Germany, Chi-t 1-9 allergy waswidespread among fish breeders because freeze-dried chironomidlarvae were frequently used as fish food. Similar, observationswere made by Baur and Liebers (1992) who observed that peoplehandling fish food frequently suffer from asthma 99. Severalother reports indicated that chironomid bodies and scales getdisintegrated into small pieces and become airborne causingallergic respiratory diseases 100. Other reports demonstrated thatadult, as well as larva of these insects may cause respiratorydiseases in sensitized persons and larvas were found to be moreallergenic as compared to the adults 101. Haemoglobin ofchironomidae has been found to induce IgE-mediated diseases102. Nandi and coworker (2014) reported that thechironomid midges Chironomus circumdatus and Polypedilum nubifercan elicit sensitization in humans 103. The ability of the midge toinduce allergic symptoms in intensely exposed population wasinvestigated in Sudan. Where the prevalence of rhinitis and asthmawas found to be higher in green nimitti midge (Cladotanytarsuslewisi) exposed villagers 104. A similar midge species,Chironomous plumosus was found to be responsible for respiratoryallergy in 45 percent of heavily exposed atopic patients. Both adultand larval organisms were shown to contain the major allergen105. In Japan, studies confirmed that 38 percent of 303 asthmaticsin Tokyo and 58 percent asthmatic children in Toyama showedskin reactivity to different species of midge. Midge specific IgEantibodies were found in 32.4 percent and 41.9 percent of the totalpatients 106. Using various components of hemoglobin of midgelarvae including purified Chi t I, studies were undertaken toidentify T cell epitopes involved in allergen-specific stimulation ofhuman peripheral blood lymphocytes. Lymphocytes of eachpatient showed an individual stimulation pattern probably due togenetic restriction 107.
Mosquito Allergy:
The mosquito name was derived from a Spanish word, whichmeans “small fly.” It belongs to the family Culicidae. Therewere thousands of species of mosquitoes known so far, withfemales possessing the distinguishing characteristic of having atube-like mouthpart known as a proboscis. This proboscispierces the skin of the host to draw blood. Female mosquitoesrequire the nutrients mainly vitamins in blood to produce eggs.Mosquito allergies were highlighted by intense local skinsymptoms including not only erythema or bulla but also ulcer orscar with general symptoms of high fever followed by mosquitobites. Most of the cases of mosquito allergy were reported fromEast Asia and the majority of patients were found to be dying ofhemo-phagocytic syndrome 108. The reaction to mosquito bitesarises as a result of an immunologic response to proteins present inmosquito saliva. Many people who were known to be bitten bymosquitoes develop an immune response for these proteins;however, only a small proportion of them develop clinicallyrelevant allergic reactions, in common large local reactions 109.There are two main types of reaction arises as a result of mosquitobites. First is the Typical (normal) reactions in which localcutaneous reactions occurs consisting of immediate wheals orswelling with surrounding flares (redness) peaking at 20 minutes;delayed itchy and indurated (firm) papules peaking at 24 to 36hours and eventually diminish over 7 to 10 days. Second is thelarge local reaction to mosquito bites. Large local reactions were farmost common type of allergic reactions to mosquito bites. Thesewere also termed as Skeeter Syndrome; typically consisting of anitchy or even painful area of redness, warmth, swelling, andindurations that ranges from a few cm to more than 10cm indiameter. Large local reactions develop within hours of the bitewith subsequent progress by 8 to 12 hours or more and resolvewithin 3 to 10 days. Large local reactions may cover the peri-orbitalregion and much of the face or even entire face, especially in case ofan infant or child. They can further interfere with seeing, eating,drinking or normal use of extremities. Severe large local reactionscan be represented by low-grade fever and malaise. Systemicallergic reactions to mosquito bites include papular or acutegeneralized urticaria. In rare cases, severe asthma, anaphylaxis,serum sickness or lymphadenopathy, hepatosplenomegaly, feversand necrotic skin reactions at the site of mosquito bite may be seen110.
Mosquito bites can cause varying levels of local swelling, papularurticaria in case of children and rare systemic allergic reactionsreaction most often seen in children arises as a result of mosquitoand flea bites. Although, a variety of other bites have been alsoreported to be linked in smaller numbers with the occurrence ofhypersensitivity reactions. Systemic allergic reactions may arise inresponse to the mosquitos’ bites, several types of bloodsuckingflies, fleas, kissing bugs, lice and ticks 111. Sometimes, the bites ofthese insects lead to serious health problems like paralysis, malaria,encephalitis and West Nile Virus and others. These bites may alsocause life-threatening and traumatic conditions, if insect allergicpersist itself or if the causal organisms invade inside the body uponbiting the skin. Malaria, dengue, West Nile virus, chikungunya,yellow fever, filariasis, tularemia, dirofilariasis, Japaneseencephalitis, Saint Louis encephalitis, Western equine encephalitis,Eastern equine encephalitis, Venezuelan equine encephalitis, RossRiver fever and Barmah Forest fever were group of knowndisorders arises as a result of mosquitoes sting. People with neuroinvasive West Nile virus can develop conditions such asencephalitis i.e. inflammation of the brain or meningitis i.e.inflammation of the surrounding tissue of the brain. The mainsymptoms include headaches, fever, neck stiffness, disorientation,coma, tremors, seizures and even paralysis.
A number of allergic reactions to mosquito bites have also beenreported by various researchers 112,113. Allergic reactions tomosquito bites follow the classical pattern for allergic disease.Predisposed individuals with no previous exposure to mosquitogive no reaction to an initial mosquito bite but they do soonsubsequent bites 114. The reactions were usually Type I,immediate hypersensitivity responses, but may also inducedelayed local cutaneous responses 115 and even anaphylaxis.Immediate and/or delayed reactions to mosquitoes were inducedby components of the salivary secretions. Kausar and coworker(2007) reported mosquito as sources of inhalant allergens 116.They also reported the clinic-immunologic and immunochemicalcharacterization of mosquito Whole Body Extract (WBE). Therewere very few reports about mosquito body parts (such as scales,wings, particulate fragmented body parts) getting aerosolized andinhaled resulting in sensitization by genetically predisposedindividuals and causation of allergic diseases 117. MosquitospecificIgE in the sera of patients and IgE binding allergeniccomponents in the mosquito WBE (Aedes, Anopheles and Culexspecies) has been reported by Agarwal 1991 and Wu and Lan 1989117. Kausar and coworkers (2007) performed immunoblotanalysis with WBE of 3 species of mosquitoes (Culexquinquefasciatus, Aedes aegypti and Anopheles stephensi) and foundunique individual IgE-binding patterns and suggested that bothgenus and species-specific mosquito allergens exist [116].
Wasp and Bee Stings
Hymenoptera stings were the common cause of severe allergicreactions ranging from local reactions to anaphylactic shock oreven death in some cases 118. Wasps belong to the order ofHymenoptera and include ants, apids (bees and bumble bees) andvespids (wasps, hornets and yellow jackets). Allergic reactionsto Hymenoptera stings range from several local to severe systemicreactions or even death. These reactions were usually acute,beginning within minutes to hours reported in around 76–96% ofthe patients. However, there were reports of delayed responsesoccurring after several days to weeks of the event. Of the 2606reactions noted in 1964 by Academy of Allergy survey, 2.8% didnot appear until several days after the sting. There have also beenreports of neurological complications, hyperglobulinaemia,thrombocytopenic purpura, nephrotic syndrome and hepatorenalsyndrome. The neurological complications were infrequent butoften serious and include clinical manifestations damaging thecentral and peripheral nervous systems. Means et al. reported acase with relapsing and progressive course of neurologicalsymptoms and signs including bilateral weakness and numbness ofthe arms and legs followed by sting by yellow jacket (Vespulapennsylvanica) 119. The patient was found alert and orientedthroughout the clinical course, but eventually died after suddenrespiratory and cardiac arrest. Necropsy revealed massivepulmonary embolism as the cause of death. Examination of thenervous system showed areas of demyelination throughout thecentral and peripheral nervous system associated with necrosis andinflammatory infiltrates in the brain stem and spinal cord.Maltzman et al reported about two cases and reviewed other fivecases of optic neuropathy after the sting by bee and wasp 120.Most cases reports significant visual recovery after corticosteroidtreatment. Bachman et al. reported five cases with acuteinflammatory polyradiculopathy following Hymenoptera stingswith good recovery 121. Some cases had nerve biopsy, whichshowed segmental demyelination. Several serious neurologicalmanifestations and cerebral lesions of Hymenoptera stings havebeen also reported. Encephalitis 122, peripheral neuritis 123,optic neuropathy 124, myasthenia gravis 125, cerebral infraction126, acute inflammatory polyradiculopathy indistinguishablefrom Guillan-Barre 127, acute disseminated encephalomyelitis128 and encephalo-myelo-radiculoneuritis 129 all have beenreported. Means et al. 130 reported a case with relapsing andprogressive bilateral weakness and numbness of arms and legsfollowed by Vespula pennsylvanica stings. Autopsy revealed areas ofdemyelination throughout the central and peripheral nervoussystem with necrosis and inflammatory infiltration in the brainstem and spinal cord. Also, massive pulmonary embolism wasfound as a cause of death. Jin et al. (2010) reported thathyaluronidase is a minor yellow jacket venom allergen and onlyaboutb10% to 15% of patients with yellow jacket allergy wasestimated to possess IgE against the hyaluronidase protein 131 .Component-resolved diagnosis with antigen and phospholipasedetect all patients to have yellow jacket venom allergy. Witharanaet al, (2015) in Sri Lanka conducted experiments on patientsstings from 2011 to 2013. Data were gathered via a questionnaireconducted and specimens of offending insects were collected foridentification. They found that five species were available fromthose in anaphylactic shock (four Apis dorsata, one Ropalidiamarginata). Vespa tropica stinging leads to a characteristic skinlesion. They reported that the risk factors that favor the occurrenceof disorders may include day-time outdoor activities, occupation(tea plantation workers) and period of year. The period of yearhighlights pollen season when the insects were found in theabundance. Only 4.6% of patients developed anaphylactic shock.Vespa tropica stings also lead to a unique skin lesion at the site ofthe sting.
Scorpion sting
Scorpion stings were supposed to consider as a major threat forpublic health in many regions of the world especially in lessdevelopedcountries of tropics and subtropics. Fatani et al. (2010)reported that scorpion was a real problem as compared to all otherstings of insect in Saudi and Egyptian anti-venoms 132. Thescorpion venomous species cause severe systemic reactions,lymphadenitis, twitching, muscle spasm and convulsions. Thepatients might die of respiratory paralysis with pulmonary edemawithin 2 to 3 hours after being sting 133. Fetaih et al. (2013)injected experimental mice with scorpion venom 134. Theyreported most obvious changes in the liver with acute cellularswelling, hydropic degeneration, congestion of central veins andportal blood vessels. Additionally, extramedullary hematopoiesisand invaginations in nuclei of hepatic cells with formation ofintranuclear cytoplasmic inclusions were also observed 135.Local symptoms of envenomation by scorpion sting start withinseconds or minutes after inoculation at the affected site. Thesystemic symptoms develop within 45 to 60 minutes after the stingand include Central Nervous System manifestations like irritability,anxiety, hyperthermia, excitability, agitation, visual changes,nausea, vomiting, nystagmus, hyperreflexia, ataxia, hemiplegia,focal or generalized seizures and encephalopathy 136. Thescorpion toxin poorly passes through the blood-brain barrier andthe effects on the Central Nervous System were secondary to thedirect stimulation on the medullary sympathetic center 137. Therewas a sudden rise in blood pressure due to sympatheticstimulation, which can cause rupture of blood vessels, intracranialhemorrhage, encephalic infarcts, failure of the respiratory centerand even paralysis 137.
Other insects
Many reports are suggesting that mayflies may cause allergicrhinitis and asthma 32. Figley (1929) was the first to report theincidence of may fly allergy 1[32]. He reported that of the 1248atopic patients studied 7% gave skin test positivity with Mayflyextract and that 40 of these patients benefited withimmunotherapy. Pellicle was identified as body component of themayfly responsible for the allergic symptoms. Parlato (1929)reported the first case of respiratory allergy to caddis fly 33. Skintests with WBE of caddis fly resulted in immediate wheal and flarereaction in 5-7% of allergic patients. Hyposensitization(immunotherapy) of these patients with caddis fly extract resultedin good control of symptoms, particularly asthma 138-141.Osgood (1957) showed that 34.5% of his allergic patients showedmarked reactivity to caddis fly WBE, while 60% elicited moderateand 5.5% slight to negative reactions 142. Kino and coworkers(1987) found that wings of caddis fly cause sensitization inasthmatic patients. Koshte and coworkers (1989) identifiedhemoglobin to be a prominent caddis fly allergen 143 . Smith andcoworker (2005) described the prevalence of sensitization tocommonly found insects like caddis fly 144.There were several reports on inhalant allergy to various otherinsects including housefly, mushroom fly, screwworm, blowfly andfruitfly, aphids, and bugs (Hemiptera), honey bees and yellowjacket (Hymenoptera), beetles (Coleoptera), locusts and crickets(Orthoptera) 138-146. Locust feces have been reported to be mostpotent allergen and were, therefore, been used forhyposensitization of allergic patients. Further, using immunefluorescentstaining several workers suggested that the source oflocust antigen might be the peritrophic membrane that lines the gutand surrounds the feces 147.
Conclusion
It is quite evident that insects contribute clinically importantinhalant allergens to the air in respirable sized particles. Therefore,it is of interest to review information on allergens caused byinsects. However, the study on allergy caused by insects is limited.We are surrounded by a large number of other insect species and itis a potential source of inhalant allergens. Hence, we documentknown allergens caused by insects in this review.
| Country | Cause of insect allergy |
| India | Bee, Yellow jackets, hornets, wasps |
| USA | Paper Wasp, Yellow Jacket, Hornet, and European Hornet |
| UK | Wasps and Hornets |
| Japan | The Killer Hornet-Suzumebachi, Mukade-Centipede, Huntsman spider, cockroaches |
| Australia | Lxodes, Australian Jack Jumper Ant |
| Africa | Bumblebee, Humblebee, Fire ant, Harvester ant |
| Grade type | Description |
| Grade 1 | Systemic reaction is characterized by generalized urticaria or erythema, itching, malaise or anxiety |
| Grade 2 | Reactions may include symptoms associated with grade I reactions as well as generalized edema, tightness in the chest, wheezing, abdominal pain, nausea and vomiting and dizziness |
| Grade 3 | Reactions may include symptoms associated with grade I or II reactions of dyspnea, dysarthria, hoarseness, weakness, confusion and a feeling of impending down |
| Grade 4 | Reactions may include symptoms associated with grade I, II or III reaction as well as any two of the following with fall in BP, loss of consciousness, incontinence of urine or feces or cyanosis |
| Grade | Defined By | |
| Mild | Skin and subcutaneous tissues only | Generalized erythema, urticaria, periorbital edema or angioedema |
| Moderate | Featured suggesting respiratory, cardiovascular or gastrointestinal involvement | Dyspnea, stridor, wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness or abdominal pain |
| Severe | Hypoxia, hypotension or neurologic compromise | Cyanosis or SpO2 less than 92 percent at any stage, hypotension (SBP less than 90 mm Hg in adults), confusion, collapse, LOC or incontinence |
| Type of reaction | Clinical features |
| Localized stinging reaction | The majority were caused by caterpillars. |
| Cause varying degrees of pain, itchiness, weal or blister formation and rarely systemic symptoms such as dizziness, sweating, and abdominal pain. | |
| Papular, urticaria and dermatitis | Usually caused by hairs from caterpillars or moths. |
| No Lepidoptera species in NZ cause this type of reaction. | |
| Reactions range from mildly itchy, papular urticaria (small red bumps swelling) that resolves within an hour to moderately itchy, urticarial, scaly, blistering or widespread eczema-like reactions that can persist for weeks. | |
| Widespread | Some species of Lonomia caterpillars found in South America cause localized stings that may progress to a severe haemorrhagic illness. |
| Hemorrhage (bleeding) | The sting transmits venom which causes burning pain, headache, nausea or vomiting.Over the next few days widespread bleeding occurs into the skin, mucous membranes, lungs, brain. |
| Ophthalmia nodosa | This is a toxic or allergic eye irritation caused by caterpillar hairs. |
| The hairs may be windblown, transferred to the eye with a finger or other object or the caterpillar may contact the eye directly. | |
| Upper eyelid contact dermatitis usually occurs. Immediately after exposure, chemosis (swelling of the conjunctiva) develops. | |
| Dendrolimiasis and pararamose | These refer to itchy skin rashes associated with joint pain or inflammation. Cartilage may also be involved in dendrolimiasis. |
| Joint destruction and potentially deforming arthritis can results |
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