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Home , Bee sting, Caria (butterfly), Dermatobia hominis, House dust mite, Id reaction, Latrodectism

Papular Urticaria and Things that Bite in the Night Jeffrey G. Demain, MD, FAAAAI

Address external pressure, which might result in slowing of blood , & Immunology Center of Alaska, 2741 DeBarr Road, flow, thereby enhancing precipitation of immune complexes C-405, Anchorage, AK 99508, USA. [1]. might also have a more diffuse, generalized dis- E-mail: [email protected] tribution involving the torso, neck, and face. The distribu- Current Allergy and Asthma Reports 2003, 3:291–303 tion of lesions serves as an important clue in identifying the Current Science Inc. ISSN 1529-7322 Copyright © 2003 by Current Science Inc. culprit (Table 1). Papules are erythematous, rang- ing from 3 to 10 mm. In the clinical setting, lesions are often excoriated and secondarily infected, contributing to the Whether we are hiking in the back country or playing in our characteristic intense pruritis. Perennial or seasonal exacer- backyard, we run the risk of exposure to offending arthro- bations are common and are presumed to be associated pods. Papular urticaria is a very common with re-exposure to the offending arthropod. Recurrence of reaction to the bites, stings, and contact with critters such as papular urticaria with re-exposure seems to lessen in adoles- , , spiders, , mosquitoes, midges, , and even cence and adulthood. This might reflect the development of caterpillars. Children seem to be at greatest risk, although immune tolerance toward the antigenic [2,3] adults are also vulnerable. The classic presentation of papular , including mosquitoes, flies, gnats, mites, urticaria includes recurrent pruritic papules or vesicles and ticks, and caterpillars, have been linked to papular urti- varying degrees of local edema. Severity is often related to caria. Penneys et al. [4] demonstrated antibody the host response to the salivary or contactant proteins. binding to and foregut endothelial Our understanding of the immune mechanism continues to antigen in mosquitoes. Distinct stages of evolving mos- improve; however, our approach to therapy has remained quito-bite immunity have been described (Table 2): I) essentially unchanged. Although this review admittedly induction; II) delayed reaction alone; III) immediate reac- reaches beyond papular urticaria, it is with the intention of tion with delayed reaction; IV) immediate reaction alone; improving the reader’s recognition of the offending arthro- and V) lack of immediate or delayed reaction [4–7]. In pods, the characteristics of reactions, and the current thera- unexposed subjects, there is no reaction to the first bite. peutic approaches. Both the delayed and the immediate reactions account for the ensuing papular urticaria. Previously sensitized sites also erupt following the appearance of new lesions, sug- Introduction gesting that circulating antigen triggers the reactivation of Papular urticaria is a manifestation of recurrent pruritic sensitized sites [8]. papules or vesicles and varying degrees of local edema. The pathogenesis and exact immune mechanisms of pap- Reactions are thought to be the result of a hypersensitivity ular urticaria remain somewhat unclear. Heng et al. [3] reaction to , stinging, or urticating . The sev- reported granular deposits of C1q, C3, and IgM in the superfi- erity of the eruption and pruritis are related to the host cial dermal vessels in three subjects with papular urticaria, response to the salivary or contactant proteins. Children suggesting that immune complexes with complement activa- seem to be predisposed to papular urticaria; possibly a tion through the classic pathway might be involved in the reflection of immune mechanisms and/or behaviors that pathogenesis. A subsequent study by Jordaan and Schneider facilitate the encounters with the offending critters. It is no [9] of 30 patients with papular urticaria failed to demonstrate surprise that a seasonal predilection during spring and deposition of IgA, IgG, IgM, C3, or fibrin by direct immuno- summer is commonly reported, although perennial exac- fluorescence. Immunochemistry results revealed abundant T erbations also occur. lymphocytes and macrophages. Yoshikawa [10] reported the Typically, papules are grouped in clusters on exposed histology of lesions produced by Chelacaropsis spp. mites in areas, particularly extensor surfaces of extremities and con- six subjects. After 48 to 72 hours of exposure, biopsies of stricting areas such as the tops of socks and around waist- lesions revealed perivascular aggregation of mononuclear bands. In some cases, papules follow a vascular distribution. cells and slight edema of the papillary [2,3,9,10]. It has also been postulated that papules around constricted Although the lesions and pattern of papular urticaria areas might represent the effects of local factors, such as are characteristic, other conditions based on presentation 292 Allergic Dermatosis and Urticaria

Table 1. Distribution of papular urticaria as a diagnostic tool Arthropod Exposed area Ventral surfaces Constricting band (waist, sock) Generalized Yes No No No Flies Yes No No No Gnats Yes No No No Yes No No No Other mites Yes Yes Yes No TicksNoNoYesNo Yes No Yes No

Adapted from Millikan [5].

Table 2. Classification of human mosquito-bite reported as . , snakes, spiders, reaction and (in descending order) accounted for 79% of deaths from envenomation, with Texas having the highest Stage Immediate Delayed number of venomous deaths. Many deaths caused by arthro- INoNo pods go unrecognized as such because the signs of envenom- II No Yes ation are not noticed. Other arthropods, such as reduviids III Yes Yes and caterpillars, might be the source of severe toxic as well as IV Yes No allergic reactions in . VNoNo Contact with arthropods is no longer limited to endemic Adapted from McCormack et al. [7]. regions. Venomous arthropods are often transferred inad- vertently by shipments of goods. This is best demonstrated by the introduction of the imported red fire ant, Solenopsis and/or histologic features should be considered. Included invicta, into the United States from . In 1939, fire ants in the differential are atopic , , entered the United States on infested produce [19] and adverse drug reactions, “id” reaction, varicella, again, in the 1950s, they entered on an unregulated ship- rubra, polymorphous light eruption (PMLE), Giannoti- ment of azaleas [20]. The imported fire ant now infests more Crosti syndrome, linear IgA bullous dermatosis, and pityri- than 160 million acres in 13 states. Further illustrating this asis lichenoides. Features distinguishing papular urticaria point are three cases of envenomation in Michi- include distribution (clustered or grouped papules), pat- gan. Scorpions arrived as stowaways in camping equipment tern of recurrence, and histopathology [2]. from Arizona and again in infested citrus shipments from Arthropoda, “joint-footed ,” is the largest phylum Florida [21]. Worldwide travel for business, tourism, and in the animal kingdom. It accounts for approximately 80% military service has also placed offending arthropods and of the and encompasses more than 1.5 million subjects together [17,19–21,100]. described species [11]. Arthropods have a dual economic impact. They provide a source of food and pollination, but also destroy crops, food, , and shelter. The medical Arachnida impact on humans includes transmission of disease as well The class Arachnida includes 65,000 species identified by as morbidity and mortality associated with immune-medi- their four pairs of jointed legs, segmented bodies, large cepha- ated and toxic reactions after exposure to salivary protein, lothorax, and hardened (chitinized) exoskeleton. There are , excrement, or body parts. Millions of individuals several species that attack humans. invasion can provide are affected annually [11–18,100]. a meal or a site for larval development. Through envenoma- Venomous arthropods are found in every state in the con- tion or salivation, they can cause pronounced local or sys- tinental United States. In addition to papular urticaria, insects temic symptoms [21]. and arthropods are responsible for more severe, IgE-mediated reactions. These reactions can be limited to a cutaneous event, Mites such as urticaria, or cause generalized, as in life-threatening More than 30,000 species of mites and ticks make up the . IgE-mediated reactions present with immediate subclass . Of these, approximately 50 species of reactivity, usually within minutes, and are often followed by a mites are capable of causing lesions in . These subsequent, late-phase reaction, as long as several hours later. blood-feeding arthropods are important vectors of pathogens, Parrish [16] reviewed the death certificates of people whose most of which are transmitted in saliva, spreading diseases deaths were recorded as animal-related fatalities from 1950 to such as , endemic typhus, western equine 1959. He found 460 people whose cause of death was encephalomyelitis, and rickettsial pox. Cutaneous reaction to Papular Urticaria and Things that Bite in the Night • Demain 293 mites is usually papular or vesicular, with intense pruritis. The days. In addition to the patient, all family members and saliva of the has been identified as the primary source of close contacts should be treated simultaneously. Bed linen antigen that causes an immediate hypersensitivity [22]. and clothing should be washed in hot water if they are to be used within 5 days. Persistent pruritis is common owing to Scabies mite immunologic reactivity to remaining , feces, or dead Scabies is caused by the by the mite Sarcoptes sca- mites. The persistent pruritis can be managed with oral anti- biei. Causing a condition that is common in children and , cool compresses, phototherapy, and topical or infants, the mites are spread by skin-to-skin contact and can systemic . Secondary infections owing to excoriation stay alive in clothing and linen for 2 to 5 days. The female are treated with appropriate [24,25]. mite burrows into the skin, leaving a trail of eggs and fecal matter [23]. An extremely itchy usually follows a 2- to 4- Chigger mite week incubation period. Other family members are fre- Chigger mites (harvest mites, red bugs, mower’s mites, and quently infected as well, providing an excellent clue to the scrub mites) have a characteristic, bright-red coloration diagnosis. Subsequent result in an immediate, and, at 0.25 to 0.5 mm size, are barely visible to the naked intense, pruritic rash distributed in the interdigital webs, eye. They are the larvae of trombiculid mites. Dermatitis wrists, axillary folds, genitalia, and periareola region [24]. from chigger mites is second only to that from scabies mites There are several variations of the cutaneous response to sca- in causing mite-associated papular urticaria. They ascend to bies infestation. Infants present with a papulosquamous covered areas of skin that are less toughened by exposure. eruption of the head and vesicular eruptions on the feet. Their ascent is usually halted by a waistband or belt, result- Elderly and immunocompromised patients can be infested ing in their pattern involving areas of constricting clothing, with Norwegian scabies and present with diffuse, crusted, usually limited to the waist down. Chigger mites do not excoriated patches covering the entire body, including the actually suck blood, as commonly thought. Instead the mite subungual spaces. Norwegian scabies is highly contagious, secretes a salivary enzyme onto the skin, allowing feeding even with casual contact, among compromised patients [23]. on semidigested tissue and extracellular fluid. In nonsensi- Nodular lesions of the groin and axilla might erupt in 10% to tized patients, the lesions are 1- to 3-mm pruritic papules; 15% of patients with scabies [10,25]. papular urticaria, vesicles, or granulomatous reactions with The clinical presentation of scabies is thought to repre- fever and lymphadenopathy can be seen in sensitized indi- sent both local irritation and the development of a hyper- viduals. Chigger mites do not burrow into the skin, so sensitivity response. Antibody responses during scabies (S. warm, soapy water can be used to kill the remaining larvae. scabiei) infestation have been examined. Hancock [26] Symptomatic treatment with oral , cool com- demonstrated elevated IgG and IgM and lowered IgA con- presses, topical astringents, or topical creams might centrations in mite-infested subjects. Maretic [17] was able be beneficial [24,31,32]. to show immediate hypersensitivity to an extract of S. sca- biei by wheal and flare with the Prausnitz-Kustner test, Other mites indicating an IgE response to the mite antigen. Although it Follicle mites () are found in sebaceous glands is an important allergen in eczema, allergic rhinitis, and and hair follicles on normal, skin. They are asthma, mite, Dermatophagoides farinae, has not been thought to contribute to the underlying etiology of sebor- shown to produce papular urticaria [10,27,28]. Cross-reac- rheic dermatitis and . Treatment focuses on the tivity between the antigenic proteins of dust mites and sca- resultant disease process [24]. bies has been demonstrated in a study by Arlian [29]. Grain mites (straw itch mites) are a parasite of lar- Cross-reactivity between the dust mite, Dermatophagoides vae feeding on grain. The cutaneous manifestations might pteronyssinus, and other arthropods including , vary from erythematous maculopapular eruptions to varicel- , and Chironomidae, has also been established. liform lesions. Sensitized patients might also present with Using radioallergosorbent testing (RAST) and RAST inhibi- fever, malaise, and diarrhea. Treatment for skin manifesta- tion, Witteman et al. [30] demonstrated the presence of IgE tions is the same as that for chigger mites. Systemic symp- antibodies against insects in 26 of 82 (32%) of the dust toms are treated symptomatically [25,31]. mite–allergic group, but only 1 of 67 (1.5%) in the mite- There are numerous case reports of papular urticaria negative group. This cross-reactivity might play an impor- resulting from unusual mite infestation, such as exposure to tant role in the susceptibility to scabies and its clinical tropical rat mite after extermination of rats and a case of mite manifestations [22,29,30]. dermatitis in a child in California traced to bats living in the Principle treatment of scabies infestation involves killing wall [33,34]. These situations occur after the preferred host the mite and controlling pruritis. The scabacides used dies out or is eliminated, and the animal ectoparasites go in include: 5%, 6% in petrolatum, or lin- search of an alternate food source. Although it is difficult to dane 1%. Permethrin 5% is the scabacide of choice. Per- prove conclusively that a particular arthropod is responsible, methrin cream is applied to the entire body and washed off situations like these require the collaborative efforts of physi- in 8 hours. Most practitioners repeat this treatment in 7 cians, veterinarians, and professional exterminators [35]. 294 Allergic Dermatosis and Urticaria

Ticks and skin. Permethrin-treated clothing will main- There are many species associated with disease in tain effectiveness through several washings. humans. In addition to cutaneous reactions, ticks are impor- 3. Early detection: Removing ticks before they embed. tant vectors of human disease. Hard ticks () are 4. Removal: There have been various proposed tech- responsible for most tick-related diseases such as rickettsia niques for tick removal. The safest and most effective (eg, Q fever, Rocky Mountain spotted fever), borrelia (eg, technique is by using forceps to apply gentle, slow, , ), and flavivirus (tick-borne reverse traction. Applying oil, petrolatum, encephalitis). Ticks typically bite during the spring and sum- polish, or a lit match to the tick is ineffective and mer when people spend time in wooded areas. Like many might be harmful. Uncomplicated tick bites usually , ticks have barbed modified mandibles called che- resolve in 2 to 4 weeks. Reactivity related to the sali- licerae. Further facilitating firm attachment, a cement-like vary protein and the remaining mouth parts might substance is secreted, allowing the tick to attach and feed for result in a tick-bite granuloma. A tick-bite granuloma up to 7 days [23,100]. might resolve with local injection of ; Most tick bites are painless; in fact, victims are often however, surgical removal and appropriate antibiot- unaware that they have been bitten. The initial finding is a ics are often required [23,24,36]. red at the site of the bite. This might progress to an extremely pruritic, local swelling followed by the forma- Spiders tion of vesicles, and ecchymosis. and ulceration In the United States, it is estimated that there are more might occur. Most bites heal within 3 weeks; however, a than 2 million spiders in each acre of grassland. All spiders persistent nodule (tick granuloma) might last for months. are carnivorous and have fangs and venom to catch and Reactions to tick bites likely result from injected , immobilize their prey. The venom is produced and stored local irritation, or hypersensitivity. Immunologic reactivity, within glands located in the basal segment of the such as delayed, type IV Gell and Coombs reaction, will modified jaw (the chelicerae). The prey is subdued by the lead to induration and nodular formation [36]. Immedi- venomous fangs and crushed by chelicerae. The internal ate, type I Gell and Coombs reactions have also been sug- structures are predigested with proteases secreted by the gested as possible contributors to cutaneous reactions to salivary gland, and sucked through the mouth into the tick bites. The histology of tick attachment sites has been stomach. Despite having eight eyes, most spiders have poor extensively studied in cattle. Mast cells, eosinophils, and vision and rely on a sharpened sense of touch. It is esti- basophils are predominant cell types demonstrated. Addi- mated that in a spider's 1- to 3-year life span, it consumes tionally, elevated serum after infestation and a more than 2000 insects [21,38–40,100]. positive Prausnitz-Kustner test strongly suggest immediate There are approximately 100,000 species of spiders; how- hypersensitivity. It is further postulated that this immedi- ever, only 50 to 60 species are reported to bite humans. Two ate hypersensitivity is an important protective response species are responsible for most of the severe reactions in against blood-feeding arthropods [22,23,36]. humans [41]. Russell and Gertsch [42], in a letter to the edi- There have been anecdotal reports in the literature of ana- tor, stated that of 600 reported spider bites, an estimated phylaxis caused by the tick, Argas reflexus. As with the other 80% were found to be caused by other arthropods such as blood-feeding arthropods, salivary-gland antigen is responsi- ticks and reduviids. In the United States, three groups of spi- ble for the reactions [22]. Tick is another manifesta- ders are considered dangerous: the tarantulas (Theraphosidae tion. Its mechanism is not well understood, but it is thought spp.), the widow spiders ( spp.), and the recluse to be associated with a injected by the gravid tick. spiders (Loxosceles spp.). Although allergic reactions are not If the tick ( andersoni, D. variabilis) remains reported with spider bites, their can have significant attached at least 4 days, it initiates an acute, ascending lower– morbidity and mortality [11,12,38,40,41]. motor neuron paralysis, which might result in respiratory fail- ure and death. There is loss of reflexes and spared sensory Tarantula function. Treatment is removal of the tick, after which full Tarantulas, particularly those in South America, are among recovery is usually seen within 48 hours [22–24,37]. the largest spiders on earth, with a leg span of more than 22 Preventing tick bites is the most effective method of cm. Despite their frightening appearance and fierce reputa- controlling cutaneous lesions of tick bites and their related tion, they are relatively harmless to humans. Tarantulas are serious systemic diseases. wandering nocturnal predators that use their long hairs to feel their prey, compensating for poor eyesight. They have 1. Proper clothing: Long sleeves and long pants two large fangs and envenomate their victims. Most tarantu- tucked into boots. las must be attacked or handled roughly before they will bite. 2. Repellents: Permethrin- or diethyltoluamide Although their fangs can exceed 10 mm in length, the bite of (DEET)-containing repellents applied to clothing the North American tarantula is described as being similar to a mosquito bite or uncomplicated sting. There has not Papular Urticaria and Things that Bite in the Night • Demain 295

toms begin with local muscle cramps progressing to severe muscle rigidity of any or all of the skeletal muscles, particu- larly abdominal and leg musculature. This is followed by nausea, , salivation, fever, chills, diaphoresis, weak- ness, tremor, urinary retention, and, possibly, shock. Cuta- neous paresthesias, hyperactive deep tendon reflexes, flexor muscle spasms, and priapism are commonly associated signs. Mortality rates have been reported from 1% to 5%, typically among young children, elderly, and the immuno- compromised [12,24,38,42,43]. Treatment recommendations for systemic manifesta- tions include methocaramol intravenously (IV), 10% IV, and hydrocortisone. Aggressive use of analgesics is helpful in relieving muscle spasms. High-risk patients include those younger than 16 years old, those older than 60, those who are pregnant, or those with hyper- tensive heart disease. For high-risk patients and for cases of Figure 1. Brown recluse bite; necrotic arachnidism. severe , specific (Merck, West Point, PA) directed against the black widow spider venom can be been any report of severe reaction or death from a tarantula administered. This product is of equine origin, and its use is bite. It is less well recognized that many species of tarantulas associated with immediate risk of anaphylaxis as well as possess urticaria-producing hairs on the dorsal surface of the subsequent serum sickness. The neurotoxic effects are usu- . When threatened, the tarantula can raise its abdo- ally blocked by the antivenom within 1 to 2 hours. As with men and flick the fine hairs at the aggressor, causing pruritic, any foreign antisera, the package insert should be closely fol- papular eruption that might last for weeks. This is a common lowed for skin testing, proper indications, and precautions feature of the colorful tarantulas imported from Africa and [11,12,38,42–44]. Cool compresses and elevation can allevi- sold in pet stores [38,41,42,100]. ate pruritis and swelling. Other considerations include class I ointment and appropriate oral antibiotics Black widow [24,31]. The widow spider is so named for the belief that the female would devour the male following copulation. In actuality, the Brown recluse female is in a stuporous state after mating, allowing the male The brown , Loxosceles reclusa, is one of 10 spe- to spin a web around her and escape [42,43]. In the United cies of Loxosceles. It is a brown spider with short body hair States, there are three varieties of widow spider: the red widow and a characteristic dark brown, median band on the dor- in Florida, the brown widow in the southern states, and the sum of the cephalothorax in the shape of a violin, hence the black widow throughout the United States [11]. “fiddle-back” spider. It lives a secluded life under rocks, The black widow () is 6 mm in debris, and woodpiles, and in undisturbed clothing. It only diameter with a leg span of approximately 4 cm. The red bites when provoked, commonly when the victim is putting hourglass mark on the underside of the abdomen is char- on clothing or rummaging through stored material. acteristic. They generally prefer warm, dry climates and are The bite of a brown recluse produces a sharp but not web weavers. Although the venom in both the male and severe pain. Subsequent reactions might include local female is potent, the fangs of the male are too small to and vesicle formation. In severe bites, the pain penetrate human skin. The bite of the black widow is worsens thoughout a period of 8 hours, becoming almost referred to as latrodectism. The venom is an oily yellow unbearable. With progression to (necrotic fluid made up of six proteins, including a neurotoxin. This arachnidism; Fig.1), a halo of pallor initially surrounds the produces blockade of neuromuscular transmission due to bite as a result of arterial spasm; later, there is local hemol- an initial release of and catecholamines, fol- ysis and bleeding into the area, which might continue for lowed by exhaustion of the muscle [11,42,43]. several days. This is followed by sloughing of the skin, sub- There is little initial cutaneous response to envenoma- cutaneous tissue, and, possibly muscle, leaving a necrotic tion by the black widow, usually sensed as a pinprick fol- (volcanic) . This heals slowly with a great deal of scar- lowed by a dull, aching pain or numbness within 30 to 40 ring, often requiring plastic surgery. The primary dermone- minutes. Skin manifestations are slight erythema, local per- crotic factor in the venom is sphingomyelinase D, which spiration, mild edema, and possible lymphangitis. Systemic functions as a platelet-aggregating, neutrophil chemoat- symptoms from the neurotoxin typically begin within 15 tractant, and liberates thromboxane B2 [23]. Systemic reac- minutes to a few hours and last up to 48 hours. These symp- tions might also occur, including fever, weakness, nausea, 296 Allergic Dermatosis and Urticaria vomiting, arthralgia, and petechiae. Severe reactions can pions have a keen sense of hearing, and might have sound- include intravascular hemolysis, progressive jaundice, gross producing structures as well. Species from Brazil and India hematuria, and acute renal failure. Death has been rarely have been reported to produce sound by stridulation, reported, including eight cases in the United States from much like crickets [12,48,49]. 1950 to 1969 that were attributed to either disseminated The of the scorpion is situated terminally and intravascular coagulopathy or infection [12]. Treatment of contains a pair of venom glands separated by a muscular a brown recluse bite includes basic care, elevation, septum. The venom is ejected by strong muscular contrac- ice compresses to decrease venom activity, and prophylac- tions through an opening near the tip, stinging the victim tic antibiotics. Although systemic corticosteroids are not quickly and repeatedly. As with most arthropods, they usu- beneficial for cutaneous , they are considered first- ally do not sting unless provoked. The toxicity of the line therapy for the hemolytic syndrome [24,45]. Dapsone venom is extremely variable even between different genera inhibits neutrophil function and might be useful for both of the same species. This is exemplified by the Centruroides cutaneous and systemic symptoms [23,45,46]. Surgical vittatus, the common striped scorpion, whose sting results intervention should be delayed until the wound stabilizes. in sharp pain and a local wheal, unlike the C. suffusus, the Antivenom, with activity against sphingomyelinase D, has Durango scorpion, whose sting has been responsible for been developed, but is not yet available for clinical use thousands of deaths annually in . In the United [11,12,15,16,23,38,41,43,47]. States, the most dangerous scorpions are the C. sculturatus Some other spiders in the United States that have been and C. gertschei. Found primarily in southern Arizona, they implicated in human envenomation include wolf spiders are described as having little to no local effects; instead, the (Lycosa spp.), jumping spiders (Phidippus spp.), and vari- victim develops a strychnine-like reaction including trem- ous orb-weaving and garden spiders. Treatment is usually ors, twitching, and disorientation [100]. local, symptomatic care. Increased awareness that most Scorpion venom contains many biologically active arthropod bites are not inflicted by arachnids reflects the polypeptides including 2 to 3 , and enzymes importance of avoiding the casual assumption that unex- including phospholipase A, hyaluronidase, acetylcho- plained bites and unidentified arthropods are spiders. linesterase, and alkaline phosphatase. Another active com- ponent of scorpion venom appears to be a histamine- Scorpions releasing factor [50]. Because venom is extremely species Scorpions are very primitive creatures, estimated to be in and even genus specific, the antivenom is highly specific, existence for 400 million years. They are thought to have offering weak or no specific activity against different scor- been the first animal to come out of water onto land 345 pion species [51]. It is also interesting that there seems to million years ago and have undergone very little subse- be significant variability in venom consistency with succes- quent evolutionary change. This is supported by fossils that sive stings from the same animal [52]. Venom collected have been found in carboniferous rock estimated to be 325 from individual scorpions demonstrates a very wide vari- million years old [11,21,48,49]. ability in the number of stings yielding venom, volume of Scorpions are easily recognized by their distinct lob- venom per sting, protein content, and specific toxicity. ster-like features. They range in length from 1 to 20 cm. Stahnke [53] reported 75 deaths related to scorpion stings The common species in Texas, Centruroides vittatus, is in Arizona during a 37-year period. Parrish [16] reported approximately 6 to 7 cm in length. They have hard exoskel- eight deaths caused by scorpion stings in the United States etons (which they shed with growth); two powerful pinch- from 1950 to 1959; interestingly, two were attributed to ana- ing claws, a five-segment tail terminating in a bulbous phylaxis. Even the sting of C. vittatus has been linked to 4 structure; the telson, containing two poison glands; and a deaths. Scorpions in Mexico, India, Pakistan, and Africa pose prominent stinger. As with other arachnids, they have a the greatest health hazard. In the city of Durango, Mexico, the cephalothorax, abdominal segment, and four pairs of scorpion C. suffusus was considered to be a serious menace, jointed legs [15,48,49,100]. accounting for 44 deaths annually. There are only anecdotal There are an estimated 600 species in the order Scorpi- reports of anaphylaxis to scorpion venom in the literature. onida, with 40 species in the United States. They are dry- Our study at Wilford Hall Medical Center revealed strong evi- land animals, and in the Western Hemisphere might be dence of an immunologic reaction (IgE and IgG) associated found from 50 degrees north latitude to 50 degrees south with subsequent stings from the C. vittatus scorpion [54]. latitude. They are nocturnal creatures that spend much of Ongoing studies in San Antonio, Texas, conducted by the daylight hours protected from the heat under stones, Dan Moore, MD, suggest the development of IgE antibodies logs, and other shelter. Scorpions are exclusively carnivo- to scorpion venom and associated allergic reactions in addi- rous, feeding on a wide variety of live animals. They do not tion to toxic reactions (Unpublished communication). stalk or hunt. Instead, they depend on the keen sense of In general, symptoms of the more harmless species touch in their pedipalps to recognize the appropriate prey. include local swelling and discoloration, followed a few They have been demonstrated to survive for more than 9 days later by systemic fever and a scab at the sting site, months in a laboratory setting without food or water. Scor- without a resultant scar. Systemic effects include skeletal Papular Urticaria and Things that Bite in the Night • Demain 297 muscle spasms and twitching, paresthesias (particularly of epinephrine and steroids immediately following a mosquito the affected extremity, face, and tongue), impaired speech, bite. A few months later, she had a recurrence of broncho- salivation, mydriasis, respiratory distress, gastrointestinal spasm after two mosquito bites, again requiring epinephrine. distress, hypertension, and electrocardiographic evidence She was skin-test positive at 1:1000 mosquito extract and of ischemia. Deaths are not uncommon in the neurotoxin- consequently placed on “mosquito immunotherapy.” Subse- producing species [12,15,48,49]. quently, she was bitten three times by mosquitoes, all of Treatment is individualized depending on the identifica- which resulted in only minor cutaneous reactions. This is the tion of the species of scorpion (often which scorpions are only report of bronchospasm related to mosquito hypersen- endemic), the type of reaction, and the risk factors of the vic- sitivity. Two cases of systemic anaphylaxis from mosquito tim. Management of local symptoms requires elevation of the bite were reported by McCormack et al. [7]. Skin testing with extremity and ice compresses to the site. Although the role of whole-body mosquito confirmed IgE sensitivity. Immuno- steroids is controversial, they are generally recommended in therapy of mosquito whole-body extract was instituted, addition to phenobarbital IV (5–10 mg/kg for an infant and resulting in resolution of adverse reactions in one patient 1.2 gm for an adult), along with supportive care. Local injec- and attenuation of reactions in the other. tion of anesthetics might be helpful in pain management. McKiel [60] demonstrated that salivary-gland antigens Narcotics are contraindicated because they appear to enhance were responsible for the immediate and delayed skin reac- the toxicity of the venom. Since 1968, antivenom has been tions in mosquito-sensitive patients. In an early study by available from Arizona State University. Antivenom has been Hudson [61], the role of mosquito saliva in hypersensitiv- demonstrated to be extremely effective; however, it is species ity reaction was established. Hudson cut the salivary duct and genus specific [11,12,19,24,38]. of one group of mosquitoes and allowed these as well as a group of intact mosquitoes to take blood meals from mos- quito-sensitive individuals. Bites from the mosquitoes with Hexapoda / Insecta (Insects) the cut salivary ducts did not result in a cutaneous reaction, The class Hexapoda, true insects, is characterized by three whereas those from intact mosquitoes did. Shen [62] dem- pairs of legs and three distinct body segments: the head, onstrated human IgE and IgG antibodies against whole- the thorax, and the abdomen. In addition, most insects body extract and salivary-gland extract of mosquitoes. have one or two pairs of wings. This class includes most of Using the immunoblot technique, IgE and IgG antibodies the arthropods responsible for adverse reactions, particu- were detected in human sera against mosquito antigens, larly immediate hypersensitivity. Although insects can pre- although a clinical correlation was not established. cipitate direct envenomation effects, significant toxicity is Immediate, Arthus-type, and delayed reactions have been usually associated with multiple stings or bites. Those who reported as a response to mosquito bites. A case of serum work outdoors and those who are involved with outdoor sickness-like syndrome in a 62-year-old patient was reported sports or activities find that they have to share their activity by Gaig et al. [63]. Skin biopsy was consistent with leukocy- with a variety of insects. It has been shown that perspira- toclastic . Mosquito-specific IgE and IgG was tion, increased CO2 output, warmth, and movement present in the serum. As previously discussed, distinct stages attract certain insects, increasing the likelihood of interac- of evolving mosquito-bite immunity has been described tion [13,14,55,100]. (Table 1): (I) induction; (II) delayed reaction alone; (III) immediate reaction with delayed reaction; (IV) immediate Mosquitoes reaction alone; and (V) lack of immediate or delayed reac- Mosquitoes, like other members of the class Diptera, have tion [4–7]. Acute, cutaneous reactions to uncomplicated one pair of front wings, with a hind pair of small, knobbed mosquito bites are edematous, pruritic papules. Papular urti- structures referred to as halters. Included in this class are caria and granulomatous reactions might occur in sensitized mosquitoes, gnats, and flies. They require a blood meal dur- patients. Secondary infection is also a concern owing to exco- ing some stage of their development. There are more than riation of papules. Cutaneous reactions might benefit from 2500 species of mosquitoes. They represent one of the most applying cool compresses and oral antihistamines to control important vectors of pathogens in man, associated with the itching. Topical steroids might help reduce the pruritis more than 90 viral and parasitic diseases [13,22,38,56]. It is and attenuate the immune response. Recent studies suggest estimated that more than 1 million people are bitten by mos- that reactions might be attenuated by prophylactic treatment quitoes daily. Although there have not been any reported with antihistamines. Topical antibiotics, such as mupirocin cases of death attributed to hypersensitivity to mosquitoes, or bacitracin might reduce the risk of infection. As with most there are numerous reports of cutaneous allergic reactions, cases of papular urticaria, prevention with the use of repel- one report of bronchospasm, and two cases of anaphylaxis lents is optimal [7,22,64–66,67•,68]. [101•]. In addition to adverse reactions to mosquito saliva, there are also reports of allergy to the scale [57,58]. Flies and midges Gluck [59] reported a case of a 40-year-old atopic female Many species of flies and midges bite humans. Hypersensi- with asthma who developed bronchospasm and required tivity to the Diptera is frequently reported as an occupa- 298 Allergic Dermatosis and Urticaria

vae, intact, by surgical excision. Occlusion of the central hole, asphyxiating the larvae, might be effective [56,70–72].

Midges Biting midges, known as “no-see-ums,” are a common nui- sance. The 1- to 3-mm female midge is a vicious biter, attack- ing in swarms in the morning and late afternoon, resulting in multiple tiny punctures. The bites cause immediate painful papulovesicular lesions. Sensitized victims might develop an erythematous papule, indurated nodule, and urticaria. Bites from midges have also been reported to cause symptoms of rhinitis and bronchospasm. Environmental reduction of midges is difficult because the larvae and pupal stages are Figure 2. Wound from a . ground dwelling, and the metamorphosis into adults occur at irregular intervals [13,24,56,57,73]. tional allergy. A group of entomologists were surveyed, and Nonbiting Diptera such as the caddis and chironomids 21% reported “allergy” to Diptera. As with other Diptera, (red midge larvae) have also been associated with morbidity. flies are a vector for major diseases worldwide [58,100]. Caddis flies are associated with inhalant allergy from wing hairs that can easily be dislodged and become airborne. Con- Flies junctivitis, rhinitis, and asthma are the prominent features. Black flies (Simuliidae spp.) are considered to be one of the Sensitized patients have positive skin tests, RAST, passive most intolerable pests that bite humans. They have hindered transfer, and inhalant challenge [73]. Cross-reacting homolo- economic development and human inhabitation in certain gous proteins between caddis fly, shellfish, and honeybee areas along the lower Mississippi valley. The bite of a black fly have also been reported [74]. Chironomids, the larvae of non- is initially painless, because of a topical anesthetic it secretes. biting midges, commonly used by aquarists as fish food, has Eventually, the site of the bite becomes painful, erythema- been reported to cause contact dermatitis and immediate tous, and pruritic, developing into vesicles and edematous contact urticaria in sensitized individuals [75–77]. papules. The bite also causes a systemic reaction, “black fly Treatment for fly bites is primarily local wound care to fever,” precipitating headaches, fever, nausea, vomiting, mal- prevent secondary infection. Topical or intralesional steroids aise, and generalized lymphadenopathy. Black flies also are and oral antihistamines are useful in controlling the inflam- important vectors for and onchocerciasis (river matory reaction and pruritis. Appropriate antibiotics are com- blindness). Horseflies and deerflies are the most common of monly needed as therapy against [56,71]. the 3000 species of flies in the Tabanidae family. They bite viciously and deeply, resulting in immediate pain, bleeding, Fleas and, often, subsequent local infection. Bites are single, These small, wingless insects live as parasites on and although multiple bites have been reported. Additionally, mammals. Domestic animals such as cats, dogs, and birds horsefly bites might induce a wheal and flare response, and bring fleas into households. Newly emerging fleas become have also been associated with more severe systemic symp- an obligate parasite once on the host. Fleas feed by pierc- toms. More than 30 cases of allergic reactions to horsefly ing the skin of the host to extract capillary blood. Saliva is bites have been reported [57,69,100]. introduced as an anticoagulant. Fleas can survive a remark- Cutaneous myiasis is the infestation of tissue by the lar- ably long time without a host. In the absence of a host, vae of flies. Flies lay their eggs on the surface of the skin. fleas become very aggressive, provoking severe attacks on The eggs hatch, and the larvae burrow into the tissue, leav- individuals moving into an empty home previously occu- ing a central hole to provide air. Infestation is caused by pied by pets. Bites from fleas are typically below the knee, many fly species. Wound myiasis begins with flies laying especially around the ankles. fleas tend to be more eggs on open wounds. Once the eggs hatch, the larvae pene- aggressive. Hypersensitivity is reported and, as in other trate the skin and begin feeding on the necrotic tissue. In causes of papular urticaria, symptoms are more common the case of the botfly, the eggs hatch on another insect and in young children. Like mosquitoes, the human host penetrate the skin of the victim while the insect takes its appears to become desensitized. Most bites resolve blood meal. Intense pruritis is often the presenting symp- without treatment. Secondary infection might occur, tom. As the larvae grow, an erythematous, edematous pap- requiring topical or systemic antibiotics. Pruritis can be ule forms, with resultant induration. Within a few days, the treated with oral antihistamines. Local therapy with wound develops serosanguinous drainage from the central potent, class 1, topical steroids might also be helpful. hole (Fig. 2). This drainage becomes more prominent as the Effective flea elimination requires removal of all adult fleas maggots grow. Treatment focuses on the removal of the lar- as well as immature fleas [23,78,79]. Papular Urticaria and Things that Bite in the Night • Demain 299

Lice physical removal of nits and lice; 2) occlusion with petrola- Lice infestation is becoming increasingly problematic, attrib- tum; 3) physostigmine ophthalmic ointment; or 4) yellow uted to increasing resistance to current therapies. Lice invade oxide of mercury ointment. Re-infestation after successful hairy or intertriginous areas and produce an extremely pru- therapy is usually caused by re-exposure to the same sexual ritic papular rash. Although saliva has been implicated as the partner or linens. Treatment failure is usually secondary to allergen, body parts as well as feces have been included as resistance to pediculicidal agents, reported with permethrin potential offending substances. Pech [54], using intradermal and , or inadequate application to all affected areas. injections of lice feces extract and lice head extract, demon- strated an immediate skin reaction in patients previously sen- Caterpillars sitized to lice with live bites. The immediate wheal and flare Lepidoptera are “scaly, winged insects,” comprising butterflies reaction was apparent in 20 minutes. The onset of the delayed and in all stages of development. There are an esti- reaction appeared within 4 to 24 hours and lasted 24 to 72 mated 140,000 species in this class. They have a very complex hours, producing an area of redness and induration [54]. life cycle; however, a general understanding is important. Studies of bovine skin also reveal hypersensitivity reaction, After the male and female mate, the fertilized eggs are depos- revealing infiltration of neutrophil, eosinophil, and lympho- ited onto foliage, where they hatch, and the larval form (cater- cyte infiltration in skin lesions [78]. pillar) emerges. The caterpillar undergoes five or six Head lice (Pediculus humanus capitus) can be transmitted developmental molts and transformations known as instars. by direct head-to-head contact or fomites such as brushes, It is during these early developmental stages that they are a combs, or hats. Usually the only manifestation is pruritis; threat to humans. The most mature instar pupates into a however, chronic or severe infestation might result in alope- cocoon, ultimately emerging as an adult [57,83]. cia, cervical adenopathy, and secondary bacterial infection. Lepidopterism refers to the ill effects of larval and adult Head lice are identified by nits and eggs found on hair shafts. butterflies and moths resulting from inhalation, ingestion, The duration of infestation can be estimated by the distance direct contact, or envenomation. The stinging or urticating between the scalp and the location of the nits (grayish-white caterpillars excrete their venom through hollow hairs or capsules) on the shaft of the hairs. This condition is 35 spines. Erucism is a term used to describe the envenoma- times more likely in whites than in blacks [23,80,81]. tion or release of poison by the larval or caterpillar stage. Body lice (P. humanus corporis), like head lice, can be Some caterpillars have urticating hairs or nettling setae that transmitted by direct contact or through fomites such as can release venom when the terminal section is broken or clothing or bed linens. Early infestation is represented by red, brushed. During the final instar of Euproctis similis, there pruritic macules, typically on the back or axillary creases. are an estimated 2,000,000 urticating setae per caterpillar Excoriation, lichenification, postinflammatory pigment [13,15,57]. Contact results in immediate burning pain changes, and persistent urticaria can develop with chronic with radiation and a grid-like row of red punctate lesions infestation [80,81]. along the skin path of the caterpillar. Other local lesions Pubic lice (P. pubis) produce infestation that is limited to include vesicles, hemorrhagic bullae, and eventual lym- short hairs. This typically involves the pubic area; however, phangitis with lymphadenopathy [83,84]. Although no body hair, axillary hair, beards, eyelashes, and eyebrows can deaths have been reported, systemic effects can occur also become infested. This is commonly transmitted within hours, including nausea, vomiting, malaise, fever, by sexual contact, although some fomites might play a role headaches, and shock [57,85,86]. Hypersensitivity, includ- in transmission. Pruritis is usually the only symptom and ing anaphylaxis, has also been demonstrated [87]. In 1980, might take up to 30 days after infestation to develop. Small, Wirtz [58] reported that 28% of entomologists surveyed blue-gray macules (maculae cerulae) on the thighs, but- had history of arthropod allergy, and of these 67% were to tocks, and suprapubic areas are characteristic. This pigmen- Lepidoptera. Perlman et al. [88] were able to demonstrate tation is thought to be secondary to a reaction of the louse evidence of both inflammatory and allergic response to saliva with blood [81,82]. this occupational hazard. Clinical and immunologic stud- Treatment of head and body lice requires killing both ies, including in vitro procedures and direct patient testing, the adult lice and the eggs with pediculocidal agents. The confirmed IgE-mediated hypersensitivity, as well as the most frequently used agent is synthetic permethrin 1% nonspecific irritation of material from Lepidoptera. Vega et lotion or creme rinse. A single application should be left al. [87] recently reported allergic reactions associated with on for 10 minutes and is effective in 90% of cases. A second exposure to the pine processionary caterpillar (Thaumeto- application is recommended after 7 days. All contacts are poea pityocampa) in Spain. Fifty-five patients with cutane- treated. Nits can be combed out of the hair. All intimate ous, ocular, or respiratory symptoms, and/or anaphylaxis fomites, such as linens, clothing, towels, and hats must be after exposure in a pine forest inhabited by the pine pro- washed with hot water and dried on high heat [23,81,82]. cessionary caterpillar were studied. Skin prick testing with Treatment of pubic lice requires the same pediculicidal whole-body extract was positive in 32 of 55 symptomatic agent described above. Eyelid infestation is treated by: 1) subjects (58%) and only 1 of 30 controls. Specific IgE 300 Allergic Dermatosis and Urticaria detection by ELISA (enzyme-linked immunosorbent assay) Diagnosis of caterpillar dermatitis is often made by the was inconsistent, presumably owing to the low amount of characteristic, grid-like pattern of erythematous punctures. antigen in the crude extract. Microscopic examination of a skin scraping might also reveal McGovern [85] reported an epidemic of stings from the the typical barbed setae of the caterpillar. Treatment of cuta- puss caterpillar in Texas during the summer of 1958. Based neous reactions is limited to symptomatic care. Washing the on the responses of 601 physicians surveyed, the natural affected areas with soapy water will help reduce cutaneous history and symptoms were described in a reported 2130 pathology. Application of cool compresses, calamine lotion, stings. The major symptoms were severe local pain (98%) and oral antihistamines might reduce pruritis. Topical or sys- and local swelling (92%). Other symptoms included lym- temic corticosteroids might also be helpful [84,89]. Sus- phadenopathy and headache, as well as shocklike symp- pected systemic allergic reactions should be treated in the toms in 5% and convulsions in 0.2% of patients. Eight same manner as any anaphylaxis. Precautions should be patients were hospitalized, but there were no reported taken to reduce exposure by wearing gloves, long sleeves, deaths [85]. In the summers of 1972 and 1973, there was a masks, and eye protection when working in endemic areas. significant increase in the Douglas fir tussock , result- ing in devastation of 890,000 acres of forests in Oregon, Beetles Washington, and Idaho [57]. The windborne spread of the There are more than 250,000 species of beetles, making this caterpillar hairs resulted in symptoms including pruritis, the largest order in the animal kingdom [90]. Only beetles urticaria, and ocular and respiratory symptoms. Loggers, containing blistering agents are important to humans. They foresters, and lumber mill workers were most affected. are characterized by a narrow prothorax, which connects the There are an estimated 50 to 150 species that have been head and the base of the wings and ranges in length from 1 to implicated in lepidopterism, representing only 0.1% of the 2 cm. Cantharidin is the substance in their bodies that pro- known species of moths and butterflies. Four species of cater- duces when it contacts with skin. Pressure exerted by pillar frequently encountered in the United States pose a clothing or by swatting the beetle on the skin is usually suffi- potentially serious threat for the sensitized victim: 1) the io cient to cause release of the blistering fluid. Reactions prima- moth caterpillar (Automeris io); 2) the saddleback caterpillar rily consist of superficial linear bullae. If suspected, promptly (Sibine stimulea); 3) the Douglas fir tussock moth caterpillar washing the affected area with soapy water prevents the for- (Orgyia pseudotsugata); and 4) the puss caterpillar or “asp” mation of vesicles. Cool compresses and topical or systemic (Megalopyge opercularis). These have all been reported as caus- steroids might be useful in severe cases. The should be ing serious occupational and problems [57,83]. left intact to reduce the chance of infection [12,15,90,100]. The io moth caterpillar, most prevalent east of the Rocky Mountains, is 5 to 8 cm long, pale green, with lateral maroon Reduviid and white stripes. At the center of each body segment is a par- The subclass is best known for the reduviid or tial row of tubercles armed with venomous black and green kissing bugs (Triatoma protracta) and bedbugs (Cimicidae spines connected to individualized poison glands [15]. They spp.). These small, nocturnal creatures are rarely seen, usu- can be found in the urticating larval stage from early spring ally biting their sleeping victims several times during the through late fall. Contact with this caterpillar produces radi- night in order to take their blood meal. They are preda- ating pain, and a pronounced but short-lived wheal sur- cious and feed exclusively on the blood of . They rounded by wide flare [13,15,83]. often live near the source of their prey, which comprises The saddleback caterpillar, found east of a diagonal line bird nests, barns, and nests of small mammals outdoors from Massachusetts through the middle of Texas, is 2 to 3 cm and crevices, cracks, clothing, or linens indoors. Bites and long and has a brown, slug-like body, covered mid-dorsally by allergic reactions from these hematophagous insects are a markings that resemble a saddle sitting on a green and white significant public health problem [15,57,91]. blanket. Along the lateral body, there are four tubercles on There are more than 4000 species of Reduviidae, of which there are stout spines connected at their bases with which approximately 10 are reported to cause severe reac- individual poison glands. They can be found in the urticating tions in humans. They are the vector for trypanosomiasis, larval stage from May to November. Envenomation occurs Chagas disease. Trypanosomes can be found in the diges- when the victim brushes vegetation infested with these cater- tive track of a small percentage of the Reduviids (T. pro- pillars. Once the spines are brushed, the tips break off, allow- tracta) in this country. Reduviids defecate on the wound ing the to flow freely onto the skin [13,15]. after feeding, allowing entry of the trypanosomes into the The puss caterpillar, or “woolly slug,” prevalent in south- victim. The incidence of Chagas disease is on the decline in eastern United States, is the of the flannel moth. The lar- the United States, probably owing to the delayed defecation vae are seen in a variety of colors ranging from white to dark patterns of this species [92]. Reduviid bugs are approxi- gray, and range in length from 2 to 3 cm. They are completely mately 1 to 3 cm long. They are flattened dorsally, enabling covered with venomous hairs, resembling tufts of cotton, or them to hide in small cracks and crevices. An elongated, neatly combed fur in the shape of a Brazil nut [15,86]. cone-shaped nose is characteristic; hence, they are often Papular Urticaria and Things that Bite in the Night • Demain 301 called “conenose bugs” [15]. Attracted to light and in the challenge by T. protracta. This is the first report of completely absence of their preferred host, they travel toward houses successful reduviid immunotherapy. and will readily feed on humans. They take flight in the Marshall et al. [97] also examined cross-reactivity among spring and summer when temperatures are higher than different species of Triatominae. They demonstrated by 20°C, and generally do not fly more than a mile. They do RAST-inhibition that binding of IgE antibodies to T. protracta not bite through clothing; therefore, reduviid bites are usu- antigen was not inhibited by salivary extracts from T. rubida, ally on the hands, arms, feet, or face, including around the T. cavernicola, T. rubrofasciata, or Rhodnius prolixus, emphasiz- lips—hence, the name “kissing bug.” Their proboscis con- ing the importance of species identification and species-spe- tains four stylets used to pierce the skin. They feed every 3 cific antigens for diagnosis and immunotherapy. The major to 4 hours, with each engorgement taking 10 to 20 minutes. salivary protein of T. protracta, procalin, has been identified Therefore, there are often multiple feeding sites. The bite is [96]. Procalin is responsible for 89% of the allergenic activity generally painless; however, when startled or swatted, redu- of T. protracta. Procalin has recently been cloned, potentially viids can inflict a painful, piercing wound. They might providing quantities of antigen for ongoing investigation, cause severe local reactions, producing necrosis and ulcer- serologic testing, and, possibly, commercially available ation similar to spider bites [15,72,91–93]. immunotherapy [96,97]. Clinical reactions to reduviid bites vary. Most victims Immunotherapy is not yet commercially available. have no reaction, and are never aware of being bitten; how- Anaphylactic reactions should be treated the same regard- ever, sensitized individuals might have episodes of noctur- less of the etiology. Environmental controls to reduce the nal anaphylaxis [93]. Studies suggest a 5% to 7% prevalence risk of additional bites are also critical. Treatment for local of Triatoma sensitivity in the United States, with as many as skin reactions is symptomatic with cool compresses and 30,000 persons in California at risk for anaphylaxis [94–96]. class 1 topical steroids. Oral antihistamines might also be Four, distinct, cutaneous reactions have been described: 1) beneficial [98]. papule with a central punctum; 2) small vesicles grouped around the bite site with edema and erythema; 3) giant urti- carial lesion with central punctum and brawny edema; and Conclusions 4) hemorrhagic nodular-to-bullous lesions [15,91]. Massive Symptomatic treatment of papular urticaria and other cutane- extremity swelling and regional lymphadenopathy have also ous reactions to “things that bite in the night” remains the been described. Systemic reactions reported by sensitized cornerstone of management. Washing involved skin individuals include generalized pruritis, urticaria, facial promptly with soapy water often removes both the ectopara- angioedema, laryngeal and glossal edema, gastrointestinal site and the offending toxic or allergenic substance. Cool distress, dyspnea, , syncope, convulsions, and compresses provide symptomatic relief of discomfort and death [13,38,57,91,92,96]. pruritis. Antihistamines remain a mainstay in reducing the In 1982, Marshall and Street [93] published a study dis- severe pruritis often accompanying papular urticaria. Quick- cussing antigen preparation, diagnosis, and immunotherapy acting antihistamines such as hydroxyzine and diphenhy- in a T. protracta–sensitive subject who had previously dem- dramine are most effective, although sedation is a major onstrated anaphylaxis to the bite of a reduviid. Serious cases concern. Newer antihistamines such as cetirizine have been of systemic anaphylaxis are caused by hypersensitivity to sal- shown to be beneficial in both symptomatic and possibly ivary components of hematophagous insects of the genus prophylactic symptom control, while reducing the risk of Triatoma. A woman with a history of anaphylaxis was desen- sedation. Prophylactic treatment with cetirizine [99] and sitized using salivary-gland extract developed for this pur- ebastine [68] in mosquito-sensitive individuals significantly pose. Success was demonstrated by T. protracta bite challenge reduces the immediate wheal and accompanying delayed and radioimmunoassay. response of papular urticaria. The use of topical corticoster- Rohr et al. [95] identified five subjects with Triatoma oids, especially potent (class 1) steroids is widely used in hypersensitivity, initiated immunotherapy, followed IgE and treating papular urticaria, although benefits are inconsistent, IgG levels, and conducted interval bite challenges. A success- and reports are anecdotal [35]. Topical doxepin might also ful program of immunotherapy for T. protracta–induced ana- reduce itching; however, it is not approved for use in children phylaxis was developed. This program included a new passive and might also cause sedation. Other topical preparations extract antigen preparation standardized by RAST inhibition. such as camphor, menthol, or praxomine might benefit some This antigen facilitated the development of a reliable skin-test [35,68,99]. Severe pruritis prompts scratching and excoriation protocol for in vivo diagnosis of T. protracta allergy. Five of the papules, setting up a risk of secondary infection. Early patients with T. protracta–induced anaphylaxis underwent a treatment with topical antibiotics such as mupirocin or baci- rapidly increasing dosage schedule of immunotherapy. The tracin is often warranted, although appropriate systemic anti- IgE and IgG antibody responses during immunotherapy were biotics are often indicated, especially in high-risk situations. followed with solid-phase radioimmunoassay. Protection Recommendations for prevention and treatment of specific against anaphylaxis was confirmed in all patients with a bite arthropods have already been discussed. 302 Allergic Dermatosis and Urticaria

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