Journal of the Egyptian Society of Parasitology, Vol. 47, No. 2, August 2017 J. Egypt. Soc. Parasitol. (JESP), 47(2), 2017: 415 – 424

A MINI-REVIEW ON SKEETER SYNDROME OR LARGE LOCAL ALLERGY TO BITES By AMR M. EL-SAYED ABDEL-MOTAGALY1, HANAA MAHMOUD MOHAMAD1 and TOSSON A. MORSY2 Military Medical Academy1, Cairo 11291 and Department of Parasitology, Faculty of Medicine, Ain Shams University2, Cairo 11566, Egypt Abstract

Skeeter Syndrome is an allergy to mosquito saliva secreted while taken a human blood meal. It is present with extreme swelling, itching, blistering, , and general , some cases develop asthma and and even threatening anaphylactic shock. Most people of all ages particularly small children, toddlers and seniors who suffer from skeeter syndrome experi- ence a very extreme reaction showed some allergic reaction level, with itching and redness. Sometimes, the swelling is painful and so extreme that the affected limb doubles in size, eyes swell shut, and the area feels hot and hard to the touch or the bite will blister and ooze. Key words: Mosquito bite, Skeeter syndrome, Differential diagnosis, Treatment, Prevention. Introduction hough the immediate reactions persist. Peo-

The reactions to mosquito bites are ple who are repeatedly exposed to bites from caused by an immunologic response to pro- the same species of mosquito eventually also teins (polypeptides) in mosquito saliva. lose their immediate reactions. The duration Many people who are bitten by mosquitoes of each of these five different stages differs, develop an immune response to these pro- depending on the intensity and timing of teins; however, only a small proportion of mosquito exposure (Reunala et al, 1994). them develop clinically relevant allergic re- These typical reactions are annoying, but actions, most commonly large local reac- should not cause undue alarm. The immuno- tions (Peng and Simons, 2007). logical basis of sensitization and natural de- Types of reactions due to mosquito bites: sensitization to mosquito bites was described There are two main types of mosquito bites in the 1990s (Peng et al, 1966). 1- Typical (normal) reactions: Typical local 2- Large local reactions to mosquito bites cutaneous reactions to mosquito bites consist (Skeeter Syndrome): Large local reactions of immediate wheals (swelling) with sur- are by far the most common type of allergic rounding flares (redness) peaking at 20 reactions to mosquito bites: 1- Large local minutes, and delayed itchy, indurated (firm) reactions (termed Skeeter Syndrome) typi- papules peaking at 24 to 36 hours, which cally consist of an itchy or even painful area diminish over 7 to 10 days. of redness, warmth, swelling and/or indura- The typical clinical course of sensitization tion that ranges from a few cm to more than and natural desensitization to the salivary 10cm in diameter. Large local reactions de- proteins injected when mosquitoes bite was velop within hours of the bite, progress over described initially in the 1940s. It evolves 8 to 12 hours or more, and resolve within 3 over months or years. People who have nev- to 10 days, 2- Large local reactions can in- er been exposed to a particular species of volve the entire periorbital region and much mosquito do not develop reactions to the ini- of the face, or an entire extremity, especially tial bites from such mosquitoes. Subsequent in an infant or child. They can interfere with bites result in the appearance of delayed lo- seeing, eating, drinking, or normal use of cal skin reactions. After repeated bites, im- extremities. Severe large local reactions can mediate wheals develop (Mellanby, 1946). be accompanied by low grade fever and ma- With further exposure, the delayed local re- laise, 3- By inspection and palpation, it can actions wane and eventually disappear, alt- be difficult to differentiate between allergic

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inflammation caused by mosquito bites and were reported as negative. In two of the inflammation caused by secondary bacterial children, radiographs were obtained to rule infection after scratching the bites. It is im- out osteomyelitis underlying the extensive portant to obtain a meticulous history of the soft tissue swelling at the site of a witnessed time of onset of the red, warm swollen area bite on an extremity (Naidu et al, 2008). at the site of a witnessed or likely mosquito An ELISA was used to measure IgE & bite in relationship to the time of the bite. IgG4 subclasses recognizing salivary gland Large local reactions typically begin within allergens of the predominant indigenous hours. Secondary bacterial typi- mosquito Aedes vexans. The salivary aller- cally begin within days and sometimes, de- gens used in the ELISA were obtained by velop an ecchymotic appearance or are asso- dissecting the salivary glands from the heads ciated with blisters, vesicles or bullae (Si- and thoraces of 370 laboratory-reared female mons and Peng, 1999). A. vexans mosquitoes and dispersing them Systemic allergic reactions: Systemic al- in 1 mL of diluent. In the children with lergic reactions to mosquito bites include Skeeter Syndrome, serum levels of IgE, papular or acute generalized urticaria, and IgG1, IgG3, & IgG4 to A. vexans salivary rarely, asthma symptoms, anaphylaxis, se- gland allergens were significantly elevated rum sickness, or lymphadenopathy, hepato- as compared with the levels in control chil- splenomegaly, fever, and necrotic skin reac- dren. In Western blotting, sera from children tions at mosquito bite sites (Engler, 2001). with Skeeter Syndrome (but not from con- Epidemiology: People at increased risk of trol children) reacted with 8 to 10 A. vexans allergic reactions to mosquito bites include: salivary gland allergens (Peng et al, 2004b). 1- Those with a high level of exposure (e.g., The IgE and IgG, especially IgG4 and IgG1, civilian or military outdoor workers), 2- In- are involved in the development of Skeeter fants and young children with low or absent Syndrome. Serum mosquito salivary gland– natural immunity, 3- Immigrants or visitors specific IgG levels correlated significantly to a geographic area where there are indige- with the size of the immediate skin reaction nous mosquitoes that they had not previous- to mosquito bites and with salivary gland– ly encountered and to which they have no specific IgE levels. Specific IgE and IgG natural immunity, and 4-Patients with pri- concentrations were significantly higher at mary or secondary immunodeficiency dis- the end of summer, as compared with levels eases (Peng et al, 2004a). at the end of the following winter after no Clinical features and pathogenesis of large exposure to mosquitoes had occurred for six local reactions: The pathogenesis of Skeeter months (Pauthner et al, 2016). Syndrome was investigated in a study of five Natural history of large local reactions: In otherwise healthy young children age two to the absence of immune deficiency, the prog- four years who developed large local reac- nosis of Skeeter Syndrome appears to be fa- tions within hours of witnessed mosquito vorable. As an example, children often con- bites, and five age-matched control children tinue to develop recurrent large local reac- who developed smaller typical reactions tions to mosquito bites for several more within hours of mosquito bites. All the chil- summers, after which the reactions cease to dren with the large local reactions had been occur. The time to resolution varies, howev- diagnosed initially with bacterial cellulitis er (Palosuo et al, 1997) and in some patients by primary care clinicians. All received sys- in northern latitudes (eg, Alaska, Canada, temic antibiotic treatment which was discon- and the Nordic countries) this natural desen- tinued after a few days when the swelling sitization may take longer to develop be- was subsiding and the blood cultures per- cause it depends on the frequency and inten- formed at the time of initial presentation sity of the patient's exposure to mosquitoes,

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which is intermittent and limited in most Bacterial cellulitis: The key information cases by the short summer season. Addition- needed to facilitate the diagnosis of Skeeter ally, it is reduced by efforts to avoid mosqui- Syndrome is the time elapsed (hours) be- toes and prevent mosquito bites (Cohen and tween a witnessed mosquito bite, or expo- George, 2013). sure to mosquitoes and a likely mosquito In a subsequent study of sera from 402 chil- bite, and the appearance of an itchy, red, dren living in the same region of Canada warm, swollen, area at the bite site. A typi- where Skeeter Syndrome was originally de- cal presentation of Skeeter Syndrome might scribed, levels of mosquito saliva-specific involve a two-year-old child who presents IgE and IgG correlated inversely with age, with a history of playing in a park and being peaked at one to six months of age, and de- exposed to mosquitoes the previous evening, creased after age five years (Peng et al, and then wakes up the next morning with an 2002). In this geographic region, only 18% itchy, red, warm swelling of the entire peri- of 1059 adult blood donors had demonstra- orbital region at the site of a mosquito bite. ble antibodies to mosquito salivary aller- In contrast, bacterial cellulitis does not typi- gens, suggesting that in most adults, sensiti- cally develop within hours of a mosquito zation had been lost and natural desensitiza- bite. Instead, it appears several days later, tion had occurred. after scratching and excoriation of the itchy Diagnosis: Skeeter Syndrome develops area at the bite site and development of a within hours of mosquito bites. Diagnosis is secondary infection (Tay et al, 2014). On the based on the time of onset of the reaction in other hand, Cellulitis is a common problem, relationship to a witnessed or likely mosqui- caused by spreading bacterial inflammation to bite, and on the physical finding of an of the skin, with redness, pain, and lym- itchy, red, warm swollen area at the site of phangitis. Up to 40% of affected people the bite (Juckett, 2013). Testing for presence have systemic illness. Gunderson and Marti- of antibodies to mosquito saliva is not prac- nello (2012) stated that erysipelas is a form tical because the only commercially availa- of cellulitis with marked superficial inflam- ble mosquito reagents are unstandardized mation, typically affecting the lower limbs whole body extracts that contain minimal and the face. The most common pathogens mosquito salivary allergens but may contain in adults are streptococci and Staphylococ- irritant proteins (Peng and Simons, 1996). cus aureus. Cellulitis and erysipelas can re- Obtaining pure mosquito salivary allergen sult in local necrosis and abscess formation. for use in skin tests and in vitro tests by dis- Around a quarter of affected people have section of mosquito salivary glands, or by more than one episode of cellulitis within 3 direct collection from living female mosqui- years. They concluded that traditional view toes, is labor-intensive and time-consuming. that cellulitis and erysipelas are primarily Such allergens are not commercially availa- due to streptococcal species, with a smaller ble. Mosquito bite challenge tests are contra- proportion due to S. aureus, and also argue indicated because of the risk of against the current distinction between cellu- transmission through a "wild" mosquito bite, litis and erysipelas in terms of the relative and the risk of causing another severe large proportion of infections due to S. aureus. local reaction in a susceptible patient (Wang Amer and Amer (2014) in Egypt reported et al, 2007). that many rare cutaneous infections of the Differential Diagnosis: The differential face, seemed irrelevant, because rare infec- diagnosis of a large local reaction to a mos- tions in certain parts of the world are com- quito bite includes bacterial cellulitis and mon in others. For instance is cutaneous large local reactions to other insect bites and leishmaniasis (CL). Also, atypical mycobac- stings. terial infection was described in the medical

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literature since the mid-1950s. The devel- Insect stings when the venom is injected opment and introduction of a rapid radio- into the victim cause a variety of reactions, metric mycobacterial detection system has ranging from local irritation to life threaten- advanced the field of mycobacteriology over ing anaphylaxis. Abdel Rahman et al. (2015) the past 20 years. Mycobacterium tuberculo- reported that hymenoptera are the third sis from other mycobacteria and enabled the largest order of insects, comprising the saw- performance of antimicrobial susceptibility flies, wasps, bees and ants. Worldwide, over testing of mycobacteria. The increased fre- 150,000 species are recognized, with many quency of atypical mycobacterial infection more remaining to be described. The name stems from advances in the diagnostic pro- refers to the wings of the insects, but the cedures concerning the infection paired with original derivation is ambiguous. The An- the prevalence of mycobacterial disease in cient Greek ὑμήν (hymen) for membrane immunocompromised patients infected with provides a plausible etymology for the term HIV. because these insects have membranous Large local reactions to other insect bites wings. However, a key characteristic of this and stings: Mosquito bites are painless, in order is that the hind wings are connected to contrast to painful bites from flies and other the fore wings by a series of hooks called insects that cause large local reactions, and hamuli. Thus, another plausible etymology painful stings from bees, wasps, yellow involves, Hymen, the Ancient Greek god of jackets, yellow hornets, white-faced hornets, marriage, as these insects have "married or fire ants that cause large local reactions. wings" in flight. Stinging insects and the Insect bites: One out of 17 deaths world- medical risk associated with their venoms wide are due to a mosquito-transmitted ar- are complex topics, and presentation of in- bovirus (yellow fever, dengue fever…etc.) formation pertaining to them requires the protozoan (malaria…etc.) or helminthes (fil- use of technical terms. The most common ariasis…etc.) (Steen et al, 2004). reactions to these stings are transient pain However, insect bites in North America and redness at the site lasting a few hours most commonly cause local inflammatory (local reaction), and exaggerated swelling reactions that subside within a few hours and lasting a few days (large local reaction). The are no more than a nuisance (Vassallo et al, most dangerous immediate reaction is ana- 2005). Generally speaking, most insect bites phylaxis, which is potentially fatal. cause local inflammatory reactions that sub- Yellow jacket, wasps and Bee: Jin et al. side within a few hours. However, more se- (2010) reported that hyaluronidase is a mi- vere local symptoms, transmission of a dis- nor yellow jacket venom allergen, and only ease-causing pathogen, and systemic allergic 10% to 15% of patients with yellow jacket reactions are also possible. Mosquito bites allergy are estimated to have IgE against the can cause varying degrees of local swelling, hyaluronidase protein. The peptide-specific papular urticaria in children, and rare sys- cross-reactivity with Api m 2 occurs in half temic allergic reactions, including anaphy- of these sera. Component-resolved diagnosis laxis. Papular urticaria is a with antigen 5 and phospholipase would de- reaction most often seen in children follow- tect virtually all patients with yellow jacket ing mosquito and flea bites, although a vari- venom allergy. Witharana et al, (2015) in Sri ety of other bites have been implicated in Lanka conducted on patients presenting to smaller numbers of reports. Systemic aller- Base Hospital Deniyaya with suspected bee gic reactions can occur in response to the and wasp stings from 2011 to 2013. Data bites of mosquitoes, several types of blood- were gathered using a questionnaire and sucking flies, fleas, kissing bugs, lice, and specimens of offending insects collected for ticks Morsy, 2012). identification. They found that five speci-

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mens were available from those in anaphy- lymphadenopathy, with or without fever. lactic shock (four Apis dorsata, one Ropalid- The patients were treat-ed with carbolic acid ia marginata). Vespa tropica stinging (1:25). Besides, the oral anti-histamine (H1) caused a characteristic skin lesion. They and systemic antibiotics were indicated in added that the risk factors included day-time the complicated cases. In the concrete hous- outdoor activities, occupation (tea plantation es of the patients, a huge number of the large wor-kers) and period of year. The latter may ants (mainly Catagliphus bicolar) were be due to pollen season when the insects are found moving here and there, particularly in found in abundance. Only 4.6% of patients animal house included indoors. Spreading or developed anaphylactic shock. Vespa tropi- burning dried leaves of camphor tree proved ca stings led to a unique skin lesion. to an effective repellent for the ants. Ant allergy: Ants have been called “chem- Scorpion sting: Scorpion stings pose a con- ical factories” (Morgan, 2008), since the siderable threat for public health in many re- venom of some ants may contain as many as gions of the world, especially in less- devel- 75 different components (Hoffman, 2010). oped countries of tropics and subtropics. A Potiwat and Sitcharungsi (2015) in Thailand list of high risk areas includes: Saharan Af- reported that hypersensitivity reactions rica, Sahelian Africa, South Africa, the Near caused by ant stings are increasingly recog- and Middle East, South India, Mexico, and nized as an important cause of death by ana- South Latin America, to the east of the An- phylaxis. Only some species of ants (e.g. des. Cumulatively, a total of 2.3 billion per- Solenopsis spp., Myrmecia spp., and Pachy- sons are exposed to scorpion stings. Fur- condyla spp.) caused allergic reactions. Ant thermore, scorpions inhibit also the south venom contains substances, including acids areas of the Unites States and Southern Eu- and alkaloids, that cause toxic reactions, and rope (Kluz-Zawadzka et al, 2014). An esti- those from Solenopsis invicta or the import- mated 1.2 million persons are stung by scor- ed fire ant have been widely studied. Piperi- pion per year. Of them, ca 3,250 persons dine alkaloids and low protein contents can (0.27%) die. In fact, an actual incidence is cause local reactions (sterile pustules) and unknown as the majority of scorpion stings systemic reactions (anaphylaxis). Imported occur in less-developed countries, in remote fire ant venoms are cross-reactive; for ex- rural areas, jungles and deserts, remaining ample, the Sol i 1 allergen from S. invicta unreported (Chippaux and Goyffon, 2008). has cross-reactivity with yellow jacket phos- Molaee et al. (2014) in Iran reported that the pholipase. The Sol i 3 allergens is a member scorpion activity in Dezful County is a cli- of the antigen 5 families that has amino acid matological-dependent phenomenon. sequence identity with vespid antigen 5. In Egypt, not less than 100 authors dealt They concluded that management of ant hy- with scorpion. Farghly and Ali (1999) and persensitivity can be divided into immediate Meki et al. (2003) stated that the scorpion as (epinephrine, corticosteroids), symptomatic a real environmental health problem in Up- (antihistamines, bro-nchodilators), support- per Egypt mainly among the pre-school and ive (fluid resuscitation, oxygen therapy), and school aged children. The major fatty acids preventive in the he-patopancreas were oleic, linoleic (resting avoidance and immunotherapy) and Palmitic acids (Abul-Fadl, 1960). Engel- treatments. Sanad et al. (2002) in Egypt re- mann and Hallof (2004) considered the ported that individuals from the suburb of scorpions as one of the medical occupational Benha City and some adjacent villages were problem in Egypt's early times. They were presented with various degrees of skin aller- responsible for precautionary measures gy; particularly children who spend the night against epidemics and for curing snake and (sleep) on the floor suffered generalized scorpion bites. They created the first medical

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papyri and established the legal foundation date compound for further development of for the medical care of the inhabitants of microbicide against HIV-1. Also, Ding et al. Egypt by royal order. Morsy (2009) in (2015) in China reported that BmKTT-2 was Toshka District reported about 18 species of the first Kunitz-type human plasmin inhibi- scorpions Fatani et al. (2010) reported that tor from scorpion venom, providing novel scorpion was a real problem and compared insights into drug developments targeting between the protective effects of Saudi and human plasmin protease. Egyptian anti-venoms. The scorpion venom- Spider bite: Generally, Spiders are found ous species cause severe systemic reactions, worldwide on every continent except lymphadenitis, twitching, muscle spasm and for Antarctica, and have become established convulsions. Besides, the patients may die of in nearly every habitat with the exceptions respiratory paralysis with pulmonary edema of air and sea colonization. As of November within 2 to 3 hours after being sting (Efrati, 2015, at least 45,700 spider species, & 113 1949). Shoukry and families were recorded. However, there has Fetaih et al. (2013) injected experimental been dissension within the scientific com- mice with scorpion venom. They found that munity as to how all these families should the most obvious changes in the liver were be classified, as evidenced by the over 20 acute cellular swelling, hydropic degenera- different classifications that have been pro- tion, congestion of central veins and portal posed since 1900 (Foelix, 1996), While the blood vessels. Besides, extramedullary hem- venom of a few species is dangerous to hu- atopoiesis and invaginations in nuclei of he- mans, scientists are now researching the use patic cells, with formation of intranuclear of spider venom in medicine and as non- cytoplasmic inclusions were observed. Mo- polluting pesticides. Spider silk provides a hammad et al. (2014) evaluated demograph- combination of lightness, strength and elas- ic and clinical characteristics as well as out- ticity that is superior to that of synthetic ma- comes in referred children to Assiut Univer- terials, and spider silk genes have been in- sity Children Hospital during the year 2012 serted into mammals and plants to see if the- with a history of scorpion sting. They con- se can be used as silk factories. Wide range cluded that more than half of stung children of behaviors, spiders have become common had a severe clinical presentation and about symbols in art and mythology symbolizing one fifth died and that aggressive treatment various combinations of patience, cruelty regimens were recommended for such pa- and creative powers. Fear of spiders is called tients to improve the outcome. Ahmed et al. arachnophobia. (2015) reported that endocrinological chan- All possible symptoms include: itching ges were common in all children with scor- or rash, pain around the area of the bite, pion envenomation and more obvious in muscle pain or cramping, blister that’s red or cases of severe envenomation. The released purple in color, sweating, difficulty breath- mediators may account for several inflam- ing, headache, nausea and vomiting, fever, matory manifestations such as pulmonary chills, anxiety or restlessness, swollen lym- edema, myocardial failure, systemic in- ph glands, and high blood pressure. Bites flammatory response syndrome and multiple take longer to heal than insect bites, and they organ failure. The use of insulin is recom- may affect skin tissues. It’s important to mended in cases of severe envenomation to keep bite clean to reduce infection risk. improve the outcome. On the other hand, Spiders have been incriminated as causes Chen et al. (2012) in China demonstrated of human suffering for centuries, but few that peptide Kn2-7 of scorpion venom could species worldwide cause medically signifi- inhibit HIV-1 by direct interaction with viral cant envenomation dangerous to people particle and may become a promising candi- (Vetter and Isbisterm, 2008). Spiders only

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bite man in self-defense, and few produce mated protein sequencer, and by MS/ MS worse effects than a mosquito bite or bee- collision induced dissociations sting. Widow spiders occur worldwide and There were about 100 reliably reported cause latrodectism, characterized by pain deaths from spider bites in the 20th century (local and generalized) associated with non- (Williamson et al, 1996) compared to about specific systemic effects, diaphoresis, and 1,500 from jellyfish stings (Nishioka, 2001). less commonly other autonomic and neuro- Many alleged cases of spider bites may rep- logical effects (Hannum and Miller, 2008). resent false diagnoses (Isbister, 2001), made Recluse spiders are distributed mostly in the it more difficult to check the effectiveness of tropical and subtropical Western Hemisph- treatments for genuine bites (Diaz, 2004). ere and can cause severe skin lesions and Antihistamines: In randomized double- rarely systemic effects; most bites are unre- blind placebo-controlled trials of patients markable. High risky spiders in South Ame- bitten by mosquitoes in laboratory and field rica (armed spiders) and Australia (funnel- settings, prophylactic administration of a web spiders) cause rare but severe enven- non-impairing, non-sedating H1-antihistam- omation requiring medical intervention and ine, (e.g., Cetirizine, Desloratadine, Fexof- sometimes antivenom. Most other spiders enadine, Levocetirizine, or Loratadine ) re- involved in verified bites cause minor, tran- lieved itching in the early-phase allergic re- sient effects (Vetter and Barger, 2002). Fun- action and reduced the late-phase reactions nel web spiders' defensive tactics include (redness, swelling, and induration). H1-anti- fang display and their venom, although they histamines are the only class of pharmaco- rarely inject much, has resulted in 13 known logic agents that has been studied prospec- human deaths over 50 years. Australian fun- tively in prevention or treatment of large lo- nel-web spiders are generally considered the cal reactions to insect stings or bites (Ka- most dangerous spiders in the world, with rppinen et al, 2006). Patients with a non- envenomations from the Sydney funnel-web impairing, non-sedating antihistamine be spider Atrax robustus resulting in at least 14 taken on a regular daily basis when mosqui- human fatalities prior to the introduction of to exposure was inevitable, which must be an effective anti-venom in 1980 (Pineda et used to treat itching, redness, and swelling al, 2012), though this claim has also been that occur at mosquito bite sites. attributed to the Brazilian wandering spider, Short- or long-term safety of cetirizine, de- due to much more frequent accidents. Rich- sloratadine, fexofenadine, levocetirizine, and ardson et al. (2006) reported that the prote- loratadine was proved in randomized control omes of the venoms of the Brazilian wander- trials, even in young children. Safety of im- ing (armed) spiders Phoneutria nigriven-ter, pairing, sedating H1-antihistam-ines such as Ph. reidyi, & Ph. keyserlingi were compared diphenhydramine and chlorpheniramine was using two-dimensional gel electrophoresis. not well studied in controlled trials (Simons Venom components were fractionated using and Simons, 2011). a combination of preparative reverse phase Glucocorticoids: Glucocorticoids are used HPLC on Vydac C4, analytical RP-HPLC to treat the allergic inflammation associated on Vydac C8 and C18 and cation exchange with large local reactions to stinging insects. FPLC on Resource S at pH 6.1 & 4.7, or an- This approach extrapolated to the treatment ion exchange HPLC on Synchropak AX-300 of large local reactions to mosquito bites at pH 8.6. Amino acid sequences of native (Golden et al, 2011). and S-pyridyl-ethylated proteins and pep- Arthropods irritation: To reduce irritation, tides derived from them by enzymatic diges- a moderately potent topical glucocorticoid tion and chemical cleavages were deter- cream with a good benefit-to-risk ratio, for mined using a Shimadzu PPSQ-21(A) auto- example, mometasone cream 0.1%, applied

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twice daily for 5 to 10 days. For severe large Skeeter Syndrome is caused by an allergic local reactions, distressing and/or interfere reaction to mosquito saliva. These itchy, red, with normal vision, ingestion of liquid or warm swellings typically develop within food, or ambulation, an oral glucocorticoid hours of bites on the face or extremities, and as prednisone 1 mg/kg to a maximum of 50 resolve with or without treatment over 3 to mg may be given for 5 to 7 days. Many topi- 10 days. Skeeter Syndrome is commonest in cal lotions and creams with local anesthetics young children who have not yet developed and/or H1-antihistamines as diphenhydra- natural immunity to mosquitoes, and may be mine or doxepin are available for application accompanied by low-grade fever and ma- to affected mosquito bite sites; however, laise. these interventions are not recommended Skeeter Syndrome is diagnosis is clinical- because topical application of these medica- ly. The key information needed is the time tions can lead to systemic absorption and elapsed, measured in hours (not days) be- contact hypersensitivity. Antibiotic is not tween a witnessed mosquito bite or exposure indicated for Skeeter Syndrome developed to mosquitoes and a likely mosquito bite, within hours, because bacterial infection and the appearance of an itchy, red, warm, would develop within this brief time. swollen area at the bite site. Prompt recogni-

Nurse Management Guidelines tion and appropriate treatment helps avoid Allergic response: 1- Difficulty/noisy bre- unnecessary diagnostic procedures and un- athing, 2- Swelling of lips, tongue, face, ey- necessary antibiotic treatment. Skeeter Syn- es, 3- Swelling/tightness in throat, 4- Diffic- drome is frequently misdiagnosed as bacte- ulty talking and/or hoarse voice, 5- Difficul- rial cellulitis; however, Skeeter Syndrome ty swallowing, 6- Pain at bite/sting site, 7- typically develops within hours of a bite, Vomiting, 8- Abdominal pain, 9- Wheeze or and bacterial cellulitis typically develops a cough, 10- Erythema or urticarial rash, 11- few days later, after bite sites have been History of allergy to an insect bite or sting. scratched and excoriated. Clinical diagnosis Signs of envenomation/ neurotoxic paraly- of allergic reactions to mosquito bites is dif- sis: 1- Eye lids drop, 2- Decrease/eye paral- ficult because of lack of availability of high- ysis, 3- Leg weakness, 4-Abnormal respira- quality standardized allergens (mosquito sal- tion (Emerging Care Institute, 2016). ivary gland or saliva extracts) for skin tests Management:1- Remove insect and stinger or measurement of serum mosquito saliva- if still attached to skin, 2- When removing specific IgE levels. In healthy children, large stingers, use a sideways scraping motion to local reactions (Skeeter Syndrome) typically avoid further envenomation, 3- Inspect pa- cease to occur within a few years. tient’s clothing and remove any other insects Environmental measures to limit mosquito and stingers, 4- Apply a cold pack at 20 mi- breeding habitats and repellents to prevent nute on / off intervals for pain relief and to bites are the primary means of preventing reduce swelling, 5- Provide further analgesia large local reactions in patients with a histo- as required according to pain scale, 6- ry of past reactions. If mosquito exposure is Administration of tetanus toxoid as immun- predictable or inevitable, recommends a ization history, 7- Document assessment non-impairing, non-sedating H1-antihistam- findings, interventions and outcomes. ine, taken before spending time outdoors

Conclusion and Recommendations (Grade 1B). Treatment of large local reac- People bitten by mosquitoes become sensi- tions to mosquito bites is symptomatic: Pa- tized to salivary allergens, but few develop tients with bothersome itching; recommend- mosquito allergy, most commonly large lo- ed an oral non-impairing, non-sedating H1- cal reactions to mosquito bites. Systemic antihistami-ne (Grade 1B). Cetirizine, at age reactions, including anaphylaxis, are rare. appropriate doses for patients with swelling

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