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1 56 2 57 3 Tropical dermatology: Venomous arthropods and 58 4 human skin 59 5 60 6 61 7 Part I. Insecta 62 8 63 9 Vidal Haddad,Jr,MD,PhD,a Jo~ao Luiz Costa Cardoso,MD,b Omar Lupi,MD,PhD,c 64 10 and Stephen K. Tyring,MD,PhDd 65 11 Botucatu, Manaus, and Rio de Janeiro, Brazil, and Houston, Texas 66 12 67 13 68 14 CME INSTRUCTIONS 69 15 70 The following is a journal-based CME activity presented by the American reflect the official policy of the American Academy of Dermatology. The information provided in 16 Academy of Dermatology and is made up of four phases: this CME activity is for continuing education purposes only and is not meant to substitute for the 71 independent medical judgment of a healthcare provider relative to the diagnostic, management 17 1. Reading of the CME Information (delineated below) and treatment options of a specific patient’s medical condition. 72 18 2. Reading of the Source Article 73 3. Achievement of a 70% or higher on the online Case-based Post Test Disclosures 19 4. Completion of the Journal CME Evaluation Editors 74 The editors involved with this CME activity and all content validation/ 20 CME INFORMATION AND DISCLOSURES 75 peer reviewers of this journal-based CME activity have reported no 21 Statement of Need: relevant financial relationships with commercial interest(s). 76 22 The American Academy of Dermatology bases its CME activities on the 77 Academy’s core curriculum, identified professional practice gaps, the Authors 23 educational needs which underlie these gaps, and emerging clinical The authors of this journal-based CME activity have reported no relevant 78 24 research findings. Learners should reflect upon clinical and scientific financial relationships with commercial interest(s). 79 25 information presented in the article and determine the need for further Planners 80 26 study. The planners involved with this journal-based CME activity have 81 Target Audience: reported no relevant financial relationships with commercial interest(s). 27 Dermatologists and others involved in the delivery of dermatologic care. The editorial and education staff involved with this journal-based CME 82 28 Accreditation activity have reported no relevant financial relationships with commer- 83 29 The American Academy of Dermatology is accredited by the Accreditation cial interest(s). 84 30 Council for Continuing Medical Education to provide continuing medical Resolution of Conflicts of Interest 85 31 education for physicians. In accordance with the ACCME Standards for Commercial Support of 86 AMA PRA Credit Designation CME, the American Academy of Dermatology has implemented mech- 32 The American Academy of Dermatology designates this journal-based anisms, prior to the planning and implementation of this Journal-based 87 33 CME activity for a maximum of 1 AMA PRA Category 1 CreditsÔ. CME activity, to identify and mitigate conflicts of interest for all individ- 88 34 Physicians should claim only the credit commensurate with the extent of uals in a position to control the content of this Journal-based CME activity. 89 35 their participation in the activity. Learning Objectives 90 AAD Recognized Credit After completing this learning activity, participants should be able to 36 This journal-based CME activity is recognized by the American Academy diagnose, treat, and help prevent noninfectious cutaneous injuries from 91 37 of Dermatology for 1 AAD Credit and may be used toward the tropical insects. 92 American Academy of Dermatology’s Continuing Medical Education 38 Date of release: September 2012 93 Award. 39 Expiration date: September 2015 94 Disclaimer: Ó 40 The American Academy of Dermatology is not responsible for statements made by the author(s). 2012 by the American Academy of Dermatology, Inc. 95 41 Statements or opinions expressed in this activity reflect the views of the author(s) and do not http://dx.doi.org/10.1016/j.jaad.2012.04.048 96 42 97 43 98 44 Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, 99 45 for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths). Pararama is 100 46 a unique form of erucism seen in workers in contact with rubber trees in the Amazon, and it is caused by 101 47 Premolis larvae, resulting in progressive periarticular fibrosis, ankylosis, and the loss of articulation. Ants 102 48 and aquatic insects of the Belostomatidae family can cause painful bites and stings. Anaphylactic shock and 103 49 death can result from the venom of bees and wasps. Beetles can cause vesicular dermatitis via cantharidin 104 50 or paederin. Myiasis results from fly larvae (maggots) feeding on live or necrotic tissue of humans or other 105 51 hosts, while New World screwworm fly larvae feed only on living tissue and burrow (ie, screw) more 106 52 deeply when attempts are made to remove them. Tungiasis is characterized by very pruritic and painful 107 53 papules and ulcers resulting from a Tunga flea penetrating the host’s skin. Dermatologists should be able to 108 54 diagnose and treat the cutaneous manifestations of these tropical insects and educate their patients on 109 55 prevention. ( J Am Acad Dermatol 10.1016/j.jaad.2012.04.048.) 110

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111 166 112 Key words: bites; envenomation; infestations; insects; stings; tropical dermatology. 167 113 168 114 169 115 170 Terrestrial arthropods are d Pararama, caused by 116 171 divided into several classes, CAPSULE SUMMARY contact with Premolis 117 172 the most important for der- larvae, can cause peri- 118 d 173 matology is the class Insecta, Erucism is envenomation by caterpillars. articular fibrosis and 119 174 comprising around 60% of d ankylosis 120 Pararama is a unique form of erucism 175 the arthropod species in the that is characterized by severe joint 121 1,2 Injuries caused by lepi- 176 world. Whereas many in- 122 involvement. 177 sects are recognized as vec- dopterans are called erucism 123 d Lepidopterism is dermatitis caused by 5-7 178 tors of tropical diseases and lepidopterism. 124 moths. Although envenomation by 179 associated with significant 125 d caterpillars (erucism) is very 180 morbidity and mortality (eg, Injuries from ants or aquatic insects can 126 frequent, they have only 181 mosquitoes, sand flies, tsetse result from stings and/or bites. 127 rarely been studied because 182 flies, etc), other insects cause d The venom of bees and wasps may 128 of low reporting, which hin- 183 cutaneous injury via venom, produce anaphylactic shock and death. 129 ders a complete understand- 184 vesicants, and allergens. This 130 d Cantharidin or paederin from beetles can ing of the problem. It is not 185 review covers tropical insects 131 cause vesicular dermatitis. known exactly how the cat- 186 causing injury not involving 132 d erpillar venom acts. 187 an infectious agent. The most common manifestation of 133 bedbug bites is severe pruritus. Pathology is attributed to 188 134 fluids from the hemolymph 189 d Myiasis may occur from fly larvae feeding 135 and the secretion of the spic- 190 on necrotic or living tissue, but New 136 CLASS INSECTA ules, with histamine being 191 World screwworm larvae burrow deeply 137 Among the insects, there the main component identi- 192 into living tissue, causing more severe 138 are some orders which are fied thus far. Forms of adult 193 injury. 139 closely related to envenoma- moths can also cause derma- 194 140 tion and various human dis- d Tungiasis is characterized by pruritic titis (lepidopterism). 195 141 Q2 eases, such as the orders papules and ulcers. Lepidopterism occurs 196 142 Lepidoptera (butterflies and through the bristles of the 197 143 moths), Hymenoptera (ants, Hylesia genus (Saturniidae 198 144 bees and wasps), Coleoptera family); under certain conditions, this genus experi- 199 145 (beetles), Diptera (flies and ences population explosions in rural areas and 200 146 mosquitoes), Hemiptera (bugs), Dictyoptera (cock- during the rainy and warmer months in tropical 201 147 roaches, praying mantis, and termites), Phthiraptera areas.8-11 Females in the reproductive period ap- 202 3 148 (lice), and Siphonaptera (fleas). Injuries by venom- proach light sources and release ‘‘clouds’’ of bristles 203 149 ous and poisonous insects are associated mainly with from their abdomens; these can penetrate human 204 150 moths and their larvae, ants, bees, beetles, bedbugs, skin and cause an irritating dermatitis (Figs 1 and 2). [F2-4/C]205 4 151 and stink bugs. There appears to be toxins in the bristles,9,10 but the 206 152 simple penetration of the spikes seems to cause 207 153 inflammatory reactions. The irritation is severe, 208 154 Lepidoptera (moths and caterpillars) manifested by erythematous papules, swelling, and 209 155 Key points itching just a few hours after contact. Occasionally, 210 156 d Contact with Lonomia caterpillars can cause conjunctivitis, keratitis, and iritis can be observed, 211 157 Q3 a potentially fatal hemorrhagic syndrome which undoubtedly are associated with the popular 212 158 213 159 214 Q1 From the Departments of Dermatology at the Universidade Funding sources: None. 160 Q9 Estadual Paulista,a Viral Brazil Hospital, Instituto Butantan and Accepted for publication April 12, 2012. 215 161 Marine School of Biology, Botucatu; Fundacao de Medicina Reprint requests: Stephen K. Tyring, MD, PhD, Center for Clinical 216 162 Tropical do Amazonas,b Manaus; Universidade Federal do Studies, University of Texas Health Science Center, 451 N Texas 217 163 Estado do Rio de Janeiro and Policlinica Geral do Rio de Ave, Houston, TX 77598. E-mail: [email protected]. 218 c ddd 164 Janeiro, Immunology Section, Faculdade de Medicina, Uni- Published online . 219 versidade Federal do Rio de Janeiro, Brazil; and the University 0190-9622/$36.00 165 of Texas Health Science Center,d Houston, Texas. 220

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221 272 222 273 223 274 224 275 225 276 226 277 227 278 228 279 229 280 230 281 231 282 232 283 233 Fig 2. Lepidopterism. Typical erythematous papules 284 234 caused by Hylesia moths on exposed areas in 2 children 285 235 that slept in an outdoor environment 1 day before the 286 236 observation and saw the moths attracted by a light. 287 237 Photograph courtesy of Jo~ao Luiz Costa Cardoso, MD. 288 238 289 239 belief that ‘‘the dust of the wings of moths can blind a 290 240 person.’’ Accompanied by intense pruritus, they heal 291 241 7 to 14 days after symptom onset. The histopatho- 292 242 logic examination reveals a foreign body reaction 293 243 with granulomas. The use of oral antihistamines is 294 244 indicated for the control of pruritus, and topical Fig 3. Erucism. Erythema and mild edema in patients that 295 245 treatment with cold compresses, baths, and cortico- suffered injuries by Megalopigidae caterpillars. The pain is 296 246 steroid creams is recommended.10,11 always more important than the inflammation. Photograph 297 247 Erucism (from the Greek erucae [larvae]) is the courtesy of Vidal Haddad Jr, MD. 298 248 term used for envenomation caused by contact with 299 249 larval forms of moths.5-7 The majority of problems 300 250 caused by lepidopterans start with inflammatory 301 251 dermatologic manifestations of acute onset that oc- 302 252 cur by action of toxins.5,6 The manifestations occur 303 253 predominantly in the skin, depending on the inten- 304 254 sity and extent of contact. There is initially local pain, 305 255 mild to moderate erythema, edema, and occasional 306 [F3-4/C] local pruritus (Fig 3). There are characteristic in- 307 256 farcted and painful regional lymph nodes. In the first 308 257 24 hours, the lesions may progress to blistering and, 309 [F4-4/C] more rarely, necrosis in the area of contact (Fig 4). 310 258 Injuries associated with erucism have intense and 311 259 prolonged pain as the primary symptom. The man- Fig 4. Erucism. Superficial skin necrosis observed after 312 contact with a Saturniidae caterpillar. Photograph courtesy 260 ifestations regress in 24 to 48 hours.5,6 The main 313 of Vidal Haddad Jr, MD. 261 families of Lepidoptera that cause erucism are 314 262 Megalopygidae, Arctiidae, and Saturniidae. 315 263 The Megalopygidae have body setae with venom genera and species. These colors often mimic the 316 [F5-4/C] (Fig 5). The most important genera are Podalia and plants the caterpillars inhabit. The important genera 317 264 Megalopyge. Larvae of these genera have 2 types of are: Automeris, Dirphia, and Lonomia, the latter of Q4 318 265 bristles: the true venomous bristles, which are which causes a potentially fatal hemorrhagic syn- 319 266 smaller and pointed and contain the basal venom drome from contact with colonies of caterpillars in 320 267 glands, and the longer bristles, which are colorful fruit trees.5 321 268 and harmless. The caterpillars of the family Contact with Lonomia caterpillars (Fig 7) results in [F7-4/C]322 269 Saturniidae have ‘‘thorns’’ and pointed branches an intense fibrinolytic action similar to disseminated 323 270 resembling small pine trees, with venom glands at intravascular coagulation, which causes major and 324 [F6-4/C] the apices (Fig 6). They are colorful, with green potentially fatal bleeding, with extremely low plasma 325 271 shades, spots, and stripes that vary in individual levels of fibrinogen, plasminogen, and other 326

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327 381 328 382 329 383 330 384 331 385 332 386 333 387 334 388 335 389 336 390 337 391 338 392 339 393 340 394 341 395 342 396 343 397 344 398 345 399 346 400 347 401 Fig 5. Erucism. Megalopigidae caterpillars. Note the great 348 402 number of body setae or bristles. Photograph courtesy of Fig 7. Erucism. The caterpillars of the Lonomia genus 349 Vidal Haddad Jr, MD. 403 350 (Saturniidae family) are gregarious animals capable of 404 causing severe envenomation with hematologic compli- 351 405 cations and occasionally, the death of the victim. Photo- 352 graph courtesy of Vidal Haddad Jr, MD. 406 353 407 354 408 355 409 356 410 357 411 358 412 359 413 360 414 361 415 362 416 363 417 364 418 365 419 366 Fig 6. Erucism. Saturniidae caterpillars. The ‘‘pine trees’’ 420 367 bristles are characteristic of this family. Photograph cour- 421 368 tesy of Vidal Haddad Jr, MD. 422 369 423 370 424 coagulation factors. At the point of contact, the initial Fig 8. Erucism. Skin bleeding showing the coagulation 371 disorders caused by envenomation after contact with 425 symptoms resemble those caused by other lepidop- 372 Lonomia catterpillars. Photograph courtesy of Jo~ao Luiz 426 373 teran larvae, showing inflammatory phenomena. Costa Cardoso, MD. 427 The presence of ecchymosis and suffusion indicates 11,12 428 374[F8-4/C] bleeding that is either local or systemic (Fig 8). most often identified species); these larvae live in 429 375 The differential diagnosis can be made by clinical rubber trees and are seen only in the Amazon region 430 376 history, agent identification, and observation of (Fig 9). The caterpillars’ venomous bristles penetrate [F9-4/C]431 bleeding disorders. The treatment uses antilonomic into the hands of victims who collect bowls of tree 377 13,14 432 378 serum, which is present in liquid form. sap, causing initial manifestations that do not differ 433 379 Pararama is a disease that is caused by the larvae from those caused by other venomous caterpillars. In 434 380 of the Premolis species (Premolis semirufa is the some individuals, the swelling persists after 2 or 3 435

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436 491 437 492 438 493 439 494 440 495 441 496 442 497 443 498 444 499 445 500 446 501 447 502 448 Fig 10. Tocandira or bullet ant (Dinoponera spp). The 503 sting of this ant is very painful and causes systemic mani- 449 504 festations. Photograph courtesy of Vidal Haddad Jr, MD. 450 505 451 Fig 9. Pararama. Above: Premolis semirufa, the pararama 506 caterpillar near to a rubber bowl in a sap tree. The bristles 452 507 of this larvae causes severe inflammation and ankylosis in Hymenoptera (ants and bees) 453 the fingers of the hands of workers of the sap tree (right). Key points 508 454 Note the severe alterations in the radiographic examina- d Bullet ants (Paraponera species) have the 509 455 Q6 tion. Photograph courtesy of Ronaldo Monteiro Costa, MD. most painful sting of any member of the 510 456 Hymenoptera order 511 457 days, and there is a progressive periarticular fibrosis d Fire ants can cause injury simultaneously 512 458 that leads to ankylosis and a loss of function of from bites and stings 513 459 articulation.15,16 The likely mechanism for the fibro- d A massive number of bee stings can result in 514 460 sis and ankylosis is the presence of toxins that multiple organ failure because the venom is 515 461 inactivate total and C2 complement and promote a rich in phospholipases 516 462 chronic inflammation with granulomas (foreign Ants. Ants from the order Hymenoptera belong 517 463 body reaction) in deep tissues (synovial membrane, to the family Formicoidea. Injuries caused by stings 518 464 cartilage, and bone). The first contact does not or bites of ants are part of everyday life, especially for 519 465 provoke sequelae; the process occurs after repeated the inhabitants of rural areas. There are 3 subfamilies 520 466 injury, suggesting an immunologic action for its of medical importance.17,18 521 467 development.4 The subfamily Ponerinae includes the important 522 468 The diagnosis of erucism is simple when the genus Paraponera19 and their close relatives, the 523 469 victims bring in the responsible animal. With the Dinoponera. These ants may reach several centime- 524 470 exception of certain caterpillar types (eg, Lonomia ters in length, have dark coloration, and live either 525 471 and Premolis), the envenomation has a good prog- alone or in pairs in rotting wood and fallen logs, etc 526 472 nosis and the manifestations fade in 2 to 3 days (Fig 10). They are found in South and Central [F10-4/C]. 473 without major complications or sequelae. The ther- America. They are commonly called bullet ants, 527 474 apy of choice for envenomation by caterpillars is tocandiras, Cape Verdean, or 24-hour ants; the latter 528 475 local blockade with 2% lidocaine. Because the term is probably associated with the intense and 529 476 injuries usually occur on the upper limbs, local prolonged pain caused by the sting. Ponerinae ants 530 477 anesthesia easily controls the symptoms.5,6 In some inject venom through a stinger attached to an ab- 531 478 refractory cases, successive applications of anes- dominal venom gland.17-19 The pain associated with 532 479 thetic are necessary. As an additional measure, the the bullet ant’s sting is reported to be greater than 533 480 site can be washed, and compresses applied with that of any other member of the Hymenoptera order. 534 481 cold water and topical steroids with oral antihista- The pain is rated 41 on the Schmidt Sting Pain Index. 535 482 mines, which reduce inflammation but not pain.5-7 Poneratoxin is a paralyzing neurotoxin isolated from 536 483 Envenomation by Lonomia requires hospitalization, the venom that affects voltage-dependent sodium 537 484 and there is a serum antivenom produced at the ion channels and blocks synaptic transmission.20 538 485 Butantan Institute in S~ao Paulo, Brazil. Unexplained Otherwise, the venom is a poorly studied protein 539 486 bleeding after contact with caterpillars guides the mix that is used by Amazon Indians for control of 540 487 diagnosis, and the cases can be found in Central and rheumatic pains and also used in rituals of some 541 488 South America. Pararama arthritis is a sequela pro- Indian tribes in the Amazon, who place their hands 542 489 gressing to total disability of the joints of the hand, into a container full of ants to test themselves in the 543 490 and little can be done for the victim. face of intense pain. 544

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545 598 546 599 547 600 548 601 549 602 550 603 551 604 552 605 553 606 554 607 555 608 556 609 557 Fig 11. Pseudomyrmex ants or ‘‘novice’s ants’’ (Triplaris Fig 12. Red fire ant (Solenopsis invicta). This vicious ant 610 spp). These ants live naturally in trees, and their stings attacks anything that comes near the anthill with painful 558 611 cause intense pain and moderate local inflammation. stings. Photograph courtesy of Vidal Haddad Jr, MD. 559 Photograph courtesy of Vidal Haddad Jr, MD. 612 560 613 561 In subfamily Dorilinea, the Eciton genus (army also a major economic problem both because of 614 562 ants) can cause human injuries. They travel through damage to livestock and to crops. Fire ants are 615 563 the jungles of the Amazon in thousands of individ- notoriously difficult to eradicate, even self- 616 564 uals, preying and eating small live animals.17,18 The assembling into waterproof rafts to survive floods.22 617 565 stings of Eciton ants are moderately painful and there On the other hand, fire ants are not known to carry 618 566 are no studies about the characteristics of the enven- disease, and the do consume large amounts of ticks, 619 567 omation or the composition of the venom. Leaf- fleas, and other arthropods that carry infectious 620 568 cutting ants or sauvas (Atta) do not contain venom, microorganisms. 621 569 but occasionally can cut or lacerate human skin with Ants of the Solenopsis genus have venom that 622 570 their jaws. A curious fact is that some indigenous differs from most animal venoms in that it is com- 623 571 tribes use sauvas ants (which retains the reflexes of prised of oily alkaloids. Its major fraction is solenop- 624 572 the mandibles even after the head is separated from sin A, which has a cytotoxic effect that can 625 573 the body) to approximate the edges of wounds, as degranulate mast cells. An interesting fact is that 626 574 ‘‘natural’’ sutures.17,18 10% of the venom inoculated by the ants is a 627 575 Pseudomyrmex ants can attack humans that touch nontoxic protein that can cause allergic reactions of 628 576 the ‘‘novice’s tree’’ (Triplaris spp); these ants live varying degrees. 629 577 naturally in these trees, and their stings cause intense The formation of a sterile pustule within 24 hours 630 578 pain and discrete to moderate local inflammation after the bite is associated with the sting of S invicta. 631 [F11-4/C]. (Fig 11). The problem is common in some South The mechanism of the sting of these ants is charac- 632 579 American regions and can be prevented by the teristic: the ant attaches to the skin with its jaws and 633 580 identification and avoidance of the trees.21 rotates on its axis, applying a dozen stings, if not 634 581 The subfamily Myrmicinae ants include the removed.23 Fire ants cause injury simultaneously 635 582 Solenopsis genus, the lavapes or fire ants.17,18 The from both bites and stings. The burning pain is the 636 583 black fire ant (Solenopsis richteri) comes from the main initial symptom of the injury. An urticarial, 637 584 plains of Rio Grande do Sul State (Brazil), Argentina, erythematous, extremely pruritic papule immedi- 638 585 and Uruguay, while the red fire ant (Solenopsis ately forms at the point of the sting, which in about 639 [F12-4/C]. invicta; Fig 12) originated in the Brazilian Pantanal 24 hours will lead to a sterile pustule caused by the 640 586 (a vast flooded area in the midwest of Brazil) but migration of neutrophils (Fig 13). Envenomation [F13-4/C]. 587 today is widespread throughout the southeast of with multiple stings causes important pustular man- 641 588 Brazil and, when accidentally introduced in ifestations that can be confused with other skin 642 589 Louisiana and Alabama, colonized more than half diseases.17,23 These injuries occur with small chil- 643 590 of the United States in fewer than 30 years.17,18 These dren or intoxicated individuals. In addition to the 644 591 ants are carnivorous, preying on insects, eggs, young painful symptoms common to all stings, the immu- 645 592 birds, and small mammals. Moreover, they have the nogenic capacity of protein fractions and nontoxic 646 593 potential to cause envenomation and allergic venom of the fire ants may cause allergic reactions of 647 594 reactions. varying degrees, some extremely serious, including 648 595 Fire ants are not only a major pest to humans in anaphylactic shock.23,24 649 596 the southern United States, they are moving north- The stings of ants can be aggravated by the 650 597 ward, possibly because of global warming. They are development of secondary infection at the site and 651

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652 705 653 706 654 707 655 708 656 709 657 710 658 711 659 712 660 713 661 714 662 715 663 716 664 717 665 718 666 719 667 720 668 721 669 722 670 723 671 724 672 725 673 726 674 727 675 Fig 13. Red fire ant. A red fire ant stinging a human and the sequence of the action of the 728 676 venom (an initial urticariform papule and a sterile pustule 24 hours after the sting). Photograph 729 677 courtesy of Vidal Haddad Jr, MD. 730 678 731 679 allergic reactions of varying severity. There are no 732 680 laboratory tests used in the diagnosis of envenoma- 733 681 tion. Desensitizations against allergic manifestations 734 682 caused by red fire ants (S invicta) are available in the 735 683 United States, with controversial results. 736 684 Ant stings should be treated with the administra- 737 685 tion of antihistamines (dexchlorpheniramine, pref- 738 686 erably), cold compresses to control pain, and topical 739 687 corticosteroids. Massive envenomation can be med- 740 688 icated with oral corticosteroids. Prednisone can be 741 689 initiated at a dose of 30 mg for 1 to 3 days, tapering 742 690 to 10 mg per day until the withdrawal of the 743 691 drug. Patients with a history of allergy to stinging 744 692 ants should have the same care as those allergic 745 693 to bee stings, and if possible should have a kit 746 694 available with adrenaline, antihistamines, and 747 695 corticosteroids.17,18 748 696 Bees. Bees are social hymenoptera of the Fig 14. Apiidae. A group of Africanized bees (Apis spp). 749 Photograph courtesy of Vidal Haddad Jr, MD. 697 Apiidae family that live in colonies with varying 750 [F14-4/C]. degrees of functions between individuals (Fig 14). cause potentially fatal injuries. The venom provokes 751 698 When disturbed, they attack through a stinger in the local inflammatory reactions (pain, edema, ery- 752 699 abdomen, similar to ants, which is detached from thema, papules, or plaques), toxic reactions (after 753 700 the bee with part of the digestive system, killing the multiple stings, with potential kidney failure, heart 754 [F15-4/C]. insect (Fig 15). The stingers can be seen in the skin failure, or death), and allergic reactions, which can 755 701 of the victim, and early extraction with clamps be serious, such as anaphylactic shock. Massive 756 702 decreases the amount of the venom injected and attacks became common after the hybridization of 757 703 improves the prognosis of the envenomation. Bees African and European bees, generating an aggres- 758 704 attack alone or in groups. In the latter situation, they sive hybrid that has spread across America from a 759

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760 814 761 815 762 816 763 817 764 818 765 819 766 820 767 821 768 822 769 823 770 824 771 825 772 Fig 15. Apiidae. Fatal multiple attack by Africanized bees. 826 773 Note the stingers on the skin and dead bees with the part 827 774 of the digestive tube linked to the stinger. Photograph 828 Q7 courtesy of Manoel Francisco Campos Neto. 775 829 776 830 fugitive colony in Brazil nearly 40 years ago. Bees 777 831 and wasps can cause serious injuries by allergic 778 832 phenomena. A high risk of death can result from 779 833 multiple organ failure as a result of venom, rich in 780 834 phospholipases, after a massive number of Fig 16. Paederus beetles. Vesicant beetles of the Paederus 781 835 stings.4,25 genus (top) and Epicauta genus (bottom). These beetles 782 are cosmopolitan, and typical injuries in humans can be 836 The Meloponidae family ( jataıs or irapoas~ ) are 783 observed around the world, especially in hot weather 837 stingless bees that can become stuck in the hair of the 784 regions. Photograph courtesy of Vidal Haddad Jr, MD. 838 victims when they feel threatened. In extreme cases, 785 839 they can only be removed by cutting the hair.26 786 840 The treatment of a few bee stings involves anti- linear dermatitis. ‘‘Poto-pepper,’’ ‘‘Poto-large,’’ or 787 841 histamines and corticosteroid creams. Multiple stings ‘‘donkeys’’ are beetles that belong to the Meloidea 788 842 are treated symptomatically. In attacks with multiple family, measuring 1.5 to 3.0 inches in size, with 2 789 843 stings, it is essential to carefully extract the stingers genera associated with injuries: Lytta and Epicauta. 790 844 with the venom glands still not emptied, which Both genera include beetles that feed on leaves of 791 845 modifies the prognosis of the envenomation by crops, such as tomatoes and potatoes, making their 792 846 reducing the amount of injected venom4,25; other- interaction with humans likely. One substance pro- 793 847 wise, the stingers will remain in the skin and, when duced by these animals is cantharidin, a potent skin 794 3 848 pressed, will discharge their contents, increasing the and mucous irritant. 795 849 envenomation. Anaphylactic shock should be trea- Cantharidin is a vesicant that comes from more 796 850 ted with corticosteroid injections, promethazine, and than 1,500 species of ‘‘blister’’ beetles. It is absorbed 797 851 millesimal adrenalin in emergency rooms because of into the lipid component of keratinocyte mem- 798 852 the high risk of death. branes, where it actives neutral serine proteases, 799 leading to the degeneration of desmosomes and 853 800 27 854 Coleoptera (beetles) resulting in vesicles and bullae. Cantharidin is also 801 the primary ingredient of ‘‘Spanish fly,’’ a purported 855 802 Key points 856 d aphrodisiac that is made by grinding dried ‘‘blister’’ 803 Cantharidin in ‘‘blister’’ beetles cause vesi- 857 cles and bullae by activation of neutral ser- beetles. The so-called aphrodisiac effects of canthar- 804 idin are related to its ability to produce irritation of 858 805 ine proteases, which cause degeneration of 859 desmosomes the genital track, mimicking arousal. 806 Poto and ‘‘wildfire’’ are names given to the beetles 860 d Paederin in the Paederus beetle is an amide 807 of the Paederus genus, Staphylinidae family; they are 861 808 with vesicant action which blocks mitosis by 862 acting on cellular DNA easy to recognize from the elytra (shells that protect 809 the wings) overlying the anterior portion of the 863 810 Vesicant beetles are cosmopolitan and cause dorsum of the abdomen. The cosmopolitan 864 811 injuries in every continent except the polar regions. Paederus can fly, has nocturnal habits, and is 865 812 Most of these insects belong to the Paederus genus1-4 attracted to artificial light sources, invading homes 866 [F16-4/C]. (Fig 16). In Brazil, the term poto is used for 2 different and causing linear dermatitis. They feed on plant 867 813 beetles, both causing vesicular dermatitis, also called debris and are quite common in crops of maize and 868

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869 beans. The life cycle of the beetle is long, passing 923 870 through 7 intermediate larval stages before the adult 924 871 form, multiplying at the rate of 1 cycle per year.1 925 872 The Paederus beetle produces paederin, a crys- 926 873 talline and powerful caustic amide with vesicant 927 874 action, soluble in water and alcohol, which can block 928 875 mitosis by acting on cellular DNA.4 Paederin seems 929 876 to have some differences compared to cantharidin, 930 877 causing more intense erythema and smaller vesicles 931 878 that converge and form blisters. Symptoms (burning 932 879 and itching) are more intense in injuries secondary to 933 880 Paederus injuries because human contact with these 934 881 types of secretions is generally not serious, which 935 882 contributes to the relative lack of published literature 936 883 about this disease. 937 884 First described in Indonesia in the summer of 938 885 1891, potos were already known to the Chinese for 939 886 1,200 years and already used in therapy, as shown in 940 887 a manuscript from China dating from 739 AD: the 941 888 insect has powerful venom, and when it touches the 942 889 skin, it causes swelling. The venom causes the skin to 943 890 peel and (can) completely remove tattoo marks. It 944 891 can be used as a caustic against blisters, nasal polyps, 945 892 or scurvy. The Paederus beetle is approximately 1 cm 946 893 in length.28 947 894 More than 600 species of Paederus are known 948 Fig 17. Paederus beetles. The classic herpetiform lesions 895 throughout the tropical and temperate regions of the 949 896 caused by vesicant beetles (in this case, Paederus spp) are 950 globe. About 4% of the species cataloged as localized to exposed parts of the body (top). The photo- 897 951 Paederus are recognized as causing linear dermati- graph on the bottom shows a typical pattern (the ‘‘kiss 28-31 898 tis. sign’’) caused by the contact with the venom in a skin 952 899 The toxin of Paederus fuscipes was characterized flexure. Photograph courtesy of Vidal Haddad Jr, MD. 953 900 as paederin, which differs chemically from canthar- 954 901 4,28 955 idin. The dried extracts obtained from animals insect against the skin and should be differentiated 902 25 956 maintained their activity for about 8 years. from contact dermatitis, phytophotodermatitis, var- 903 957 Injuries caused by vesicant beetles occurs in hot icella zoster, herpes simplex, pemphigus, and in- 904 1,2,31 958 and rainy months. The beetle is attracted to juries caused by caterpillars.4 905 959 artificial light sources. The discharge of secretion Lesions should be immediately and intensively 906 960 occurs when the victim tries to ward off the animal washed with clean water and soap. Some authors 907 961 and presses it against the skin, usually on the neck, advocate the use of tincture of iodine in early lesions, 908 962 face, or limbs, but any exposed areas may have because this would act as a solvent. Vesicles, crusts, 909 32 963 lesions. According to the extent and the number of and pustules should be treated with potassium 910 964 the contacts, the injury can be classified as mild, permanganate compresses (1 tablet in 4 L of water) 911 965 moderate, or severe. In the latter case, there are twice a day and corticosteroid creams. If there is 912 966 systemic manifestations, such as nausea, vomiting, secondary infection, it is necessary to use topical or 913 4 967 and fever. systemic antibiotics. 914 After the discharge of the substance, the skin 968 915 shows erythema for a day or two, accompanied by 969 916 pruritus and burning. After this period, vesicles Hemiptera (true bugs) 970 917 appear (small when the injury is caused by Key points 971 918 Paederus and large when the agent is Epicauta or d Contact with stink bugs can cause burning 972 919 Lytta), which evolve to the formation of sterile and pruritus 973 [F17-4/C]. pustules, ulcerations, and crusts (Fig 17). The lesions d The painful bite of giant water bugs causes 974 920 resolve in about a week, leaving residual erythem- tissue injury by lysophospholipids in the 975 921 atous or hyperchromic macules.28 The lesions are bug’s saliva, which cause paralysis in the 976 922 elongated or linear because of the act of rubbing the neuromuscular junction of the prey 977

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978 1031 979 1032 980 1033 981 1034 982 1035 983 1036 984 1037 985 1038 986 1039 987 1040 988 1041 989 1042 990 Fig 18. Pentatomidae. The stink bug of the Pentatomidae Fig 20. Belostomatidae. Giant water bugs of the Belosto- 1043 family recently was described as a cause of skin lesions in matidae family are responsible for painful stings in hu- 991 1044 humans. Photograph courtesy of Vidal Haddad Jr, MD. mans. Photograph courtesy of Vidal Haddad Jr, MD. 992 1045 993 The treatment is similar to that used after contact with 1046 994 Paederus or cantharidin, although there is no infor- 1047 995 mation on the pharmacologic properties of sub- 1048 996 stances secreted by the Pentatomidae. 1049 997 Belastomatidae family. Venomous aquatic 1050 998 insects are rare, but the arthropods of the 1051 999 Belostomatidae family can cause painful stings in 1052 1000 humans.34-36 The Belostomatidae or giant water bugs 1053 1001 are cosmopolitan insects that live in tropical, sub- 1054 1002 tropical, and temperate areas (Fig 20). The giant [F20-4/C]. 1003 water bugs are classified in 2 main genera 1055 1004 (Lethocerus and Belostoma).35 They are found in 1056 1005 freshwater habitats, such as ponds, lakes, and rivers, 1057 1006 and are associated with an unpleasant sting that has 1058 1007 led to the name of ‘‘toe biters’’ to describe these 1059 1008 insects that may defensively attack the foot of a 1060 1009 wader or hurt someone who picks them up.35,36 1061 1010 They can often be observed feeding upon tadpoles, 1062 1011 fish, and even animals as large as ducklings. They 1063 1012 breathe in the water with a siphon tube projecting 1064 1013 from the back of their abdomen and can be found 1065 1014 hanging head down at the surface of the water, but 1066 1015 Fig 19. Pentatomidae. Inflammation caused by a sting are also highly capable swimmers.2 These Hemiptera 1067 1016 bug in a human. The lesions are similar to those caused by have popular names in Brazil, as water cockroach, 1068 1017 vesicant beetles. Photograph courtesy of Vidal Haddad Jr, water scorpion, arauemboia , bota-mesa, and finger 1069 1018 MD. stinger. 1070 1019 Giant water bugs can reach large diameters, as 1071 d Recent increases in bedbugs may be related 1020 seen in the genus Lethocerus, where insects are 1072 1021 to their resistance to insecticides and elimi- 1073 nation of their predators recorded at sizes up to 10 cm. They have a short 1022 stout beak that is used to pierce their prey and 1074 1023 Suborder Heteroptera present toxic saliva. The main species of the genus 1075 1024 Pentatomidae family. Similar to the vesicant Lethocerus in Brazil are L delpontei, L grandis, and 1076 1025 beetles, some insects of the order Hemiptera (family L maximus.35,36 1077 1026 Pentatomidae) can cause serious irritation to human The saliva of these insects is a mix of enzymes 1078 [F18-4/C]. skin (Fig 18). These insects are popularly known as capable of liquefying the tissues of the prey, but 1079 1027 marias-fedidas (‘‘stink Mary’’) and they have been there are also other toxic effects. The toxicity of the 1080 1028 recently related to vesicular and erythematous pla- saliva of these animals was studied by Picado,37 who 1081 1029 ques in the same regions affected by vesicant beetles, reported ‘‘increased clotting of blood in men and 1082 1030 which are accompanied by burning and pruritus33 animals, hemolysis similar to that associated with 1083 [F19-4/C]. (Fig 19). The differential diagnosis can be difficult. venom of snakes in rabbits but not in humans.’’

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1084 1138 1085 1139 1086 1140 1087 1141 1088 1142 1089 1143 1090 1144 1091 1145 1092 1146 1093 1147 1094 1148 1095 1149 1096 Fig 21. Belostomatidae. Erythematous papule at the point Fig 23. Cimex spp. The bites from bedbugs are not 1150 of a bite of a giant water bug. The skin signs were not accompanied by severe manifestations in nonsensitized 1097 1151 proportional to the severe pain. Photograph courtesy of persons, but they can cause notable erythema, edema, and 1098 Vidal Haddad Jr, MD. itching in those persons allergic to the bites (especially 1152 1099 atopic individuals). 1153 1100 1154 1101 other to suck blood1,2 (Fig 22). Like ticks, the [F22-4/C]. 1102 presence of inflammatory reactions at the point of 1155 1103 the bites can cause significant discomfort to the 1156 1104 victim (Fig 23). Bedbugs are found in overcrowded [F23-4/C]. 1105 areas of towns and cities, and their presence has 1157 1106 traditionally had a deep relationship with low stan- 1158 1107 dards of sanitation, but bedbugs are now reported in 1159 1108 ‘‘upscale’’ homes and hotels. One possible reason for 1160 1109 the increase in bedbugs may be the better control of 1161 1110 cockroaches, which prey on them. 1162 1111 Bedbugs were common parasites in several coun- 1163 1112 tries until the deployment of dichlorodiphenyltri- 1164 1113 chloroethane and pyrethrum insecticides in the 1165 1114 1940s. Pesticides have greatly reduced the presence 1166 1115 of these arthropods; for a long period, they were not 1167 1116 a problem for domestic environments in the 1168 1117 Americas. In recent years, a combination of factors 1169 1118 caused bedbugs to return—the most potent insecti- 1170 1119 cides have been abandoned because of the delete- 1171 1120 rious effects to the environment, the presence of 1172 1121 bugs in some poor countries has increased, and 1173 1122 Fig 22. Cimex spp. Bedbugs are a curse resurrected in 1174 modern times. Note the blood in the abdomen of the international travel has become more common. 1123 1175 parasite and lesions in the distribution of ‘‘breakfast, lunch, Other factors include recent resistance to pyrethroids 1124 and dinner.’’ Photographs courtesy of Vidal Haddad Jr, and dichlorodiphenyltrichloroethane, the ability of 1176 1125 MD, and Jo~ao Luiz Costa Cardoso, MD. the bedbugs to survive up to a year without food, and 1177 1126 the transportation of these bugs in luggage, resulting 1178 1127 Recently, there was demonstration of the presence of in numerous reports of bedbugs in European and 1179 1128 lysophospholipids in the saliva of the species American countries (especially in hotels); therapeu- 1180 1129 Belostoma anurum that can cause paralysis in the tic and preventive measures should be familiar to 1181 1130 neuromuscular junction of their prey.38 These insects dermatologists. 1182 1131 are capable of producing painful lesions in humans The most common species in Europe, the 1183 [F21-4/C]. and possibly of carrying infections39 (Fig 21). Americas, and Australia is Cimex lectularius (the 1184 1132 Cimicidae family. Recently, an old foe has common bedbug) and Cimex hemipteras, which is 1185 1133 returned with strength: the bites of bedbugs. These present in all warmer regions of earth.40 Bedbugs live 1186 1134 insects are parasites, and there have been reports of in groups (nymphs, eggs, and adults among blood 1187 1135 infestation in humans since the time of ancient droppings, which present a black coloration) in 1188 1136 Rome. They are hematophagous and have 2 blades cracks in walls or in wood (in bed frames, for 1189 1137 in the proboscis: one to inject an anesthetic and the example), behind woodwork on the wall, 1190

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1191 ventilators, and in furniture of all types. They feed by 1192 sucking the blood of victims during the night, when 1246 1193 they are attracted by CO2 and heat, moving with 1247 40 1194 great rapidity. One interesting fact is the strong and 1248 1195 offensive odor caused by 2 or 3 glands. The odor is 1249 1196 capable of repelling predators of the hemiptera. 1250 1197 Bedbugs bite exposed areas of the victim (espe- 1251 1198 cially the head, neck, and arms) and cause erythem- 1252 1199 atous and pruritic papules and macules (rarely 1253 1200 blisters) that can become infected after scratching. 1254 1201 The skin lesions show similarity with injuries caused 1255 1202 by other arthropods, such as fleas. There is a typical Fig 24. Myiasis of the scalp. Dermatobia hominis. 1256 1203 distribution of the bites, seen with sequential lesions 1257 1204 (‘‘breakfast, lunch, and dinner’’). The severity of the 1258 1205 lesions is determined by the degree of sensitivity of 1259 40 1206 the victim to the hemiptera. 1260 1207 When necessary, treatment includes antihista- 1261 1208 mines and topical steroids. Nonsensitized individ- 1262 1209 uals do not develop significant lesions or symptoms. 1263 1210 There is the possibility of secondary bacterial infec- 1264 1211 tions; therefore, it is important to apply topical 1265 1212 antibiotics. There is no proven disease transmitted 1266 1213 by the bite of bedbugs, but numerous candidate 1267 1214 pathogens can potentially be transmitted by Cimex 1268 1215 spp.41 Lesions in sensitized individuals may simulate Fig 25. Screwworm larvae. Cochliomyia hominivorax feeding on viable human tissue of the pelvis. Photograph 1269 1216 infections and envenomation. The eradication and courtesy of Michael Mays. Q8 1270 1217 prevention of bedbugs can be tried by the removal of 1271 1218 infested furniture, including those in transport vehi- 1272 1219 cles, and exercising caution in the purchase of Most fly larvae (maggots) provide a useful function 1273 1220 second-hand furniture and old building materials. in nature by eating decaying matter, and they can 1274 1221 Bedbug pesticide resistance appears to be a great even be used therapeutically. Some maggots, how- 1275 1222 problem. This resistance includes deltamethrin and ever, feed on living tissue. The general term for 1276 42 1223 bait insecticides for cockroaches. The most effec- infestation of maggots feeding on the host’s necrotic 1277 1224 tive insecticides are pyrethroids, dichlorvos, and or living tissue is myiasis (Fig 24). This problem is [F24-4/C]. 42 1225 malathion. While no infectious diseases have commonly seen in tropical countries and in travelers 1278 1226 been proven to be transmitted by bedbugs, more returning from tropical parts of the world. Botflies, 1279 1227 than 100 illnesses have been reported with bedbug- blowflies, and fleshflies are the 3 main families 1280 43 1228 related insecticide use, including 1 fatality. Almost causing myiasis in livestock and occasionally in 1281 1229 90% of the cases, including the fatality, were associ- humans. 1282 1230 ated with the use of pyrethroids and/or pyrethrins. The female human botfly, Dermatobia hominis, 1283 1231 captures one of more than 40 species of mosquitoes 1284 1232 Diptera (true flies) or muscoid flies and attaches its eggs to the vector’s 1285 1233 body. After releasing the vector, the eggs hatch while 1286 1234 Key points d the mosquito is feeding on the host and the larvae 1287 1235 Botflies indirectly cause myiasis by attaching its eggs to a mosquito or muscoid fly vector use the bite entry site. Alternatively, the eggs simply 1288 1236 drop off the muscoid fly when it lands on the skin. 1289 1237 which then transfers the eggs or larvae to the host Cutaneous myiasis usually presents as slowly grow- 1290 1238 ing nodules that resemble furuncles or as ulcers, but d The New World screwworm fly feeds on 1291 1239 myiasis may also be nasal, aural, or ophthalmic. 1292 1240 healthy tissue of livestock and humans and burrows (ie, screws) deeply into tissue Treatment of myiasis includes the use of forceps, 1293 1241 excision, or occlusion/suffocation approaches (eg, 1294 1242 Whereas flies are a nuisance throughout most of tape, nail polish, glue, or petroleum jelly). An alter- 1295 1243 the world because of their bites (eg, deer flies), native method of convincing the botfly to exit the 1296 1244 others carry infectious diseases (black flies carry skin is to apply an irritant such as chewing tobacco, 1297 1245 onchocerciasis; tsetse flies carry trypanosomiasis). snuff, or camphor oil.

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1298 known as the chigoe flea, jigger, nigua, and sand 1350 1299 flea, and is found in Central and South America, the 1351 Caribbean, Africa, and India. Treatment usually 1352 1300 involves extraction of the flea followed by antibiotic 1353 1301 therapy for secondary infections. Alternatively, cry- 1354 1302 otherapy or occlusion/suffocation can be used. 1355 1303 Many tropical insects cause morbidity and mor- 1356 1304 tality in their role as vectors for infectious diseases. 1357 1305 Other tropical insects, however, cause injury via the 1358 1306 release of venom, vesicants, irritants, or allergens, 1359 1307 etc. It is important for dermatologists to be familiar 1360 1308 with these insects and the injuries they cause in order 1361 1309 Fig 26. Tungiasis of the foot (Tunga penetrans). to initiate proper therapy and to advise the patient on 1362 1310 effective prevention. 1363 1311 The larvae of the New World screwworm fly, 1364 Cochliomyia hominivorax, feed on the healthy tis- 1312 REFERENCES 1365 1313 sue of livestock and occasionally humans. 1. Alexander JD. Arthropods and human skin. London (UK): 1366 1314 Screwworm females lay eggs in the exposed flesh Springer Verlag; 1984. 1367 1315 (eg, wounds). When the larvae hatch, they burrow 2. Goddard J. Arthropods of medical importance. Boca Raton 1368 [F25-4/C]. into surrounding tissue as they feed (Fig 25). If the (FL): CRC Press; 1993. 3. Carrera M. Insetos de interesse medico e veterinario. Curitiba 1369 1316 wound is disturbed, the larvae burrow or ‘‘screw’’ (Brazil): Editora da Universidade do Parana; 1991. 1370 1317 deeper into the tissue, which is the source of the fly’s 4. Cardoso JLC, Franc¸a FOS, Wen FH, Malaque CMS, Haddad V Jr. 1371 1318 name. The larvae are capable of causing severe tissue Venomous animals in Brazil: biology, clinic and therapeutic [in 1372 Portuguese]. S~ao Paulo (Brazil): Editora Sarvier; 2009. 1319 damage, including death of the host. Screwworms 1373 were officially eradicated from the United States in 5. Cardoso AEC, Haddad V Jr. Accidents caused by lepidopterans 1320 (moth larvae and adult): study on the epidemiological, clinical 1374 1321 1982, using the sterile insect technique, but the and therapeutic aspects [in Portuguese]. An Bras Dermatol 1375 1322 problem continues in Central and South America 2005;80:571-8. 1376 1323 and the Caribbean. Treatment of screwworm larvae 6. Haddad V Jr, Cardoso JLC. Erucismo e lepidopterismo [in 1377 Portuguese]. In: Cardoso JLC, Franc¸a FOS, Weh FH, Malaque 1324 infestation includes manually removing the maggots, 1378 debriding the necrotic tissue, and prescribing anti- CMS, Haddad V Jr, editors. Venomous animals in Brazil: 1325 biology, clinic and therapeutics. S~ao Paulo (Brazil): Editora 1379 1326 biotic therapy for secondary infections. Sarvier; 2009. 1380 1327 7. Haddad V Jr. Identification of acute diseases caused by 1381 1328 Siphonaptera (fleas) animals and plants in wild environments: contribution to 1382 dermatologic practice [in Portuguese]. An Bras Dermatol 2009; 1329 Key points 1383 d Tungiasis is associated with pruritus, pain, 84:343-8. 1330 ~ 1384 inflammation, and swelling, and results 8. Gusmao HH, Foratini OP, Rotberg A. Dermatite provocada por 1331 lepidopteros do genero^ Hylesia. Rev Inst Med Trop 1961;3: 1385 1332 from penetration of the skin by the Tunga 114-20. 1386 1333 penetrans flea 9. Cardoso JLC, Borges Filho TS, Carneiro ECG, Moraes HP. Surto 1387 d ~ 1334 Treatment of tungiasis involves extraction, de dermatite por Hylesia paulex no litoral do Estado de Sao Paulo, Bertioga, ver~ao 1990. Mem Inst Butantan 1990; 1388 1335 cryotherapy, or occlusion/suffocation of the 1389 flea followed by antibiotic therapy for sec- 52(suppl):82. 1336 10. Moreira SC, Lima JC, Silva L, Haddad V Jr. Description of an 1390 1337 ondary infections outbreak of lepidopterism (dermatitis associated with contact 1391 with moths) among sailors in Salvador, State of Bahia [in 1338 Although fleas are vectors of numerous infectious 1392 1339 Portuguese]. Rev Soc Bras Med Trop 2007;40:591-3. diseases, their most commonly recognized nonin- 11. Rocha-Pinango~ CL. Fibrinolisis producida por contacto com 1393 1340 fectious injury is their pruritic bite. Penetration of the orugas: comunicacion preliminar. Ata Cient Venezolana 1967; 1394 1341 skin by the female ectoparasitic Tunga penetrans 18:136-9. 1395 1342 flea, however, can cause severe pruritus, pain, 12. Burdmann EA, Antunes I, Saldanha LB, Abdulkader RC. Severe 1396 acute renal failure induced by the venom of Lonomia cater- 1343 inflammation, and swelling. Tungiasis, also known 1397 1344 pillars. Clinical Nephrol 1996;46:337-9. as nigua, pio, bicho de pie, and pique, is character- 13. Da Silva WD, Campos CM, Gonc¸alves LR, Sousa-e-Silva MC, 1398 1345 ized by a black dot at the center of an erythematous Higashi HG, Yamagushi IK, et al. Development of an anti- 1399 [F26-4/C]. papule surrounded by a white halo (Fig 26). venom against toxins of Lonomia obliqua caterpillars. Toxicon 1400 1346 Desquamation of the skin is seen after expansion 1996;34:1045-9. 1401 14. Rocha-Campos ACM. Caracterizac¸~ao biologica e imunoquı- 1347 of the flea during feeding. Without treatment, sec- ~ 1402 1348 mica do extrato de cerdas de Lonomia obliqua. Produc¸ao do ondary infections, tetanus, and gangrene can de- soro policlonal especıfico para uso humano [PhD thesis]. S~ao 1403 1349 velop. T penetrans is the world’s smallest flea and is Paulo (Brazil): Universidade de S~ao Paulo; 1999. 1404

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1405 15. Rodrigues MG. Efeitos danosos da lagarta ‘‘pararama’’ (Prem- 29. Piraja da Silva M. Le Paederus columbinus est vesicant. Arch 1460 1406 olis semirufa) a seringueiros no Estado do Para. Bol Fac Parasitol 1912;15:431-2. 1461 1407 Ciencias^ Agrarias do Para 1976;8:5-31. 30. Froes HP. Contribuic¸~ao ao estudo da ac¸~ao vesicante dos 1462 1408 16. Costa RM. Artropatia da pararamose: epidemiologIa, clınica e potos (coleopteros vesicantes). Jornal dos Clınicos 1934;4: 1463 modelos experimentais [PhD thesis]. S~ao Paulo (Brazil): Escola 22. 1409 Paulista de Medicina; 1991. 31. Cardoso AES, Lima Filho MR. Vesicular dermatitis induced by 1464 1410 17. Haddad V Jr, Cardoso JLC, Franc¸a FOS, Wen FH. Accidents Paederus: an outbreak in North eastern Brazil [in Portuguese]. 1465 1411 caused by ants: a dermatological problem [in Portuguese]. An An Bras Dermatol 1986;61:173-6. 1466 1412 Bras Dermatol 1996;71:527-30. 32. Diogenes MJN. Paederus contact dermatitis. Clinical and 1467 1413 18. Haddad V Jr, Medeiros CR. Acidentes por formigas. In: Cardoso epidemiological study, State of Ceara, Brazil [in Portuguese]. 1468 JLC, Franc¸a FOS, Wen FH, Malaque CMS, Haddad V Jr, editors. Rev Inst Med Trop S~ao Paulo 1994;36:59-65. 1414 Venomous animals in Brazil: biology, clinic and therapeutic. 33. Haddad V Jr, Cardoso J, Moraes R. Skin lesions caused by stink 1469 1415 S~ao Paulo (Brazil): Editora Sarvier; 2009. bugs (Insecta: Hemiptera: Pentatomidae): first report of der- 1470 1416 19. Haddad V Jr, Cardoso JLC, Morais RHP. Description of an injury matological injuries in humans. Wilderness Environ Med 2002; 1471 1417 in a human caused by a false tocandira (Dinoponera gigantea, 13:48-50. 1472 1418 PERTY, 1883) with a revision on folkloric, pharmacological and 34. Haddad V Jr. Animais aquaticos potencialmente perigosos do 1473 clinical aspects of the giant ants of the genera Paraponera e Brasil: guia medico e biologico. S~ao Paulo (Brazil): Editora 1419 Dinoponera (sub-family Ponerinae). Rev Inst Med Trop S~ao Roca; 2008. pp. 288. 1474 1420 Paulo 2005;47:235-8. 35. McCafferty W. Aquatic entomology. Boston (MA): Science 1475 1421 20. Szolajska E, Poznanski J, Ferber ML, Michalik J, Gout E, Books International, Inc; 1981. pp. 448. 1476 1422 Fender P, et al. Poneratoxin, a neurotoxin from anti venom. 36. New College of Florida web site. Aquatic hemiptera. Available 1477 1423 Structure and expression in insect cells and construction of a from: http://faculty.ncf.edu/mccord/doc/NaturalHistoryAquatic 1478 bio-insecticide. Eur J Biochem 2004;271:2127-36. Hemiptera.doc. Acessed April 2, 2009. 1424 21. Haddad V Jr, Bicudo LRH, Fransozo A. The Triplaria tree (Triplaris 37. Picado C. Estudo experimental sobre o veneno de Lethocerus 1479 1425 spp) and Pseudomyrmex ants: a symbiotic relationship with risks depontei (De Carlo) (Hemiptera, Belostomatidae). Mem Inst 1480 1426 of attacks for humans. Rev Soc Bras Med Trop 2009;42:727-9. Butantan 1936;10:303-10. 1481 1427 22. Mlot NJ, Tovey CA, Hu DL. Fire ants self-assemble into 38. Cardoso LS, Caccin P, Fully AL, Oliveira GA, Monteiro RQ, 1482 1428 waterproof rafts to survive floods. Proc Natl Acad Sci USA Pereira MH, et al. Lysophoslipids from the saliva of the aquatic 1483 2011;108:7669-73. hemipteran predator Belostoma anurum cause prey paralisia 1429 23. Amaral MD. Reac¸~ao cut^anea de indivıduos normais a picada [poster]. Annals of the XVI World Congress of the IST and X 1484 1430 de Solenopsis invicta [PhD thesis]. S~ao Paulo (Brazil): Instituto Congresso da SBTx, Recife, Brazil. Abstract 427-1, June 22, 1485 1431 de Biociencias,^ UNESP, Botucatu; 1994. 2009. 1486 1432 24. Conceic¸~ao LG, Haddad V Jr, Loures FH. Pustular dermatosis 39. Haddad V Jr, Schwartz EM, Schwartz CA, Carvalho LN. Report 1487 1433 caused by fire ant (Solenopsis invicta) stings in a dog. Vet of seven human envenomations caused by giant water bugs 1488 Dermatol 2006;17:453-5. of Belostomatidae family (Hemiptera, Heteroptera). Wilderness 1434 25. Franc¸a FO, Benvenuti LA, Fan HW, Dos Santos DR, Hain SH, Environ Med 2010;21:130-3. 1489 1435 Picchi-Martins FR, et al. Severe and fatal mass attacks by 40. Harvey WMC, Hill H. Insect pests. London (UK): H. K Lewis & Co. 1490 1436 ‘‘killer’’ bees (Africanized honey bees e Apis mellifera scutel- Ltd.; 1940. 1491 1437 lata) in Brazil: clinicopathological studies with measurement of 41. Delaunay P, Blanc V, Del Giudice P, Levy-Bencheton A, 1492 1438 serum venom concentrations. Q J Med 1994;87:169-82. Chosidow O, Marty P, et al. Bedbugs and infectious diseases. 1493 26. Haddad V Jr, Stolf HO. Acidente em ser humano provocado Clin Infect Dis 2011;52:200-10. 1439 por abelhas da famılia Meloponidae: relato de caso. An Bras 42. Yoon KS, Kwon DH, Srtrycharz JP, Hollingsworth CS, Lee SH, 1494 1440 Dermatol 1996;71:358-9. Clark JM. Biochemical and molecular analysis of deltamethrin 1495 1441 27. Moed L, Shwayder TA, Chang MW. Cantharidin revisited: a resistance in the common bed bug (Hemiptera: Cimicidae). 1496 1442 blistering defense of an ancient medicine. Arch Dermatol J Med Entomol 2008;45:1092-101. 1497 1443 2001;137:1357-60. 43. Centers for Disease Control and Prevention. Acute illnesses 1498 28. Frank JH, Kanamitsu K. Paederus, sensu latu (Coleoptera: associated with insecticides used to control bed bugs—seven 1444 Staphylinidae): natural history and medical importance. states, 2003-2010. MMWR Morb Mortal Wkly Rep 2011;60: 1499 1445 J Med Entomology 1987;24:155-91. 1269-74. 1500 1446 1501 1447 1502 1448 1503 1449 1504 1450 1505 1451 1506 1452 1507 1453 1508 1454 1509 1455 1510 1456 1511 1457 1512 1458 1513 1459 1514

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1 56 2 57 3 Tropical dermatology: Venomous arthropods and 58 4 human skin Q10 59 5 60 6 61 7 Part I. Insecta 62 8 63 a b c 9 Vidal Haddad,Jr,MD,PhD, Jo~ao Luiz Costa Cardoso,MD, Omar Lupi,MD,PhD, Q11 64 10 and Stephen K. Tyring,MD,PhDd 65 11 Botucatu, Manaus, and Rio de Janeiro, Brazil, and Houston, Texas 66 12 67 13 68 14 CME INSTRUCTIONS 69 15 70 The following is a journal-based CME activity presented by the American Academy of Date of release: September 2012 16 Dermatology and is made up of four phases: Expiration date: September 2015 71 17 1. Reading of the CME Information (delineated below) Ó 2012 by the American Academy of Dermatology, Inc. 72 2. Reading of the Source Article http://dx.doi.org/10.1016/j.jaad.2012.04.048 18 3. Achievement of a 70% or higher on the online Case-based Post Test 73 19 4. 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The Academy does not collect personal information from anyone it knows is 54 under the age of 13. 109 Learning Objectives 55 After completing this learning activity, participants should be able to diagnose, treat, Elsevier: http://www.elsevier.com/wps/find/privacypolicy.cws_home/ 110 and help prevent noninfectious cutaneous injuries from tropical insects. privacypolicy 1.e1

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111 Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, 166 112 for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths). Pararama is 167 113 a unique form of erucism seen in workers in contact with rubber trees in the Amazon, and it is caused by 168 114 Premolis larvae, resulting in progressive periarticular fibrosis, ankylosis, and the loss of articulation. Ants 169 115 and aquatic insects of the Belostomatidae family can cause painful bites and stings. Anaphylactic shock and 170 116 death can result from the venom of bees and wasps. Beetles can cause vesicular dermatitis via cantharidin 171 117 or paederin. Myiasis results from fly larvae (maggots) feeding on live or necrotic tissue of humans or other 172 118 hosts, while New World screwworm fly larvae feed only on living tissue and burrow (ie, screw) more 173 119 deeply when attempts are made to remove them. Tungiasis is characterized by very pruritic and painful 174 120 papules and ulcers resulting from a Tunga flea penetrating the host’s skin. Dermatologists should be able to 175 121 diagnose and treat the cutaneous manifestations of these tropical insects and educate their patients on 176 122 prevention. ( J Am Acad Dermatol 10.1016/j.jaad.2012.04.048.) 177 123 178 124 Key words: bites; envenomation; infestations; insects; stings; tropical dermatology. 179 125 180 126 181 127 Terrestrial arthropods are Phthiraptera (lice), and 182 128 divided into several classes, CAPSULE SUMMARY Siphonaptera (fleas).3 Injuries 183 129 the most important for der- by venomous and poisonous 184 130 matology is the class Insecta, d Erucism is envenomation by caterpillars. insects are associated mainly 185 131 comprising around 60% of d Pararama is a unique form of erucism with moths and their larvae, 186 132 the arthropod species in the that is characterized by severe joint ants, bees, beetles, bedbugs, 187 133 world.1,2 Whereas many in- involvement. and stink bugs.4 188 134 sects are recognized as vec- 189 d Lepidopterism is dermatitis caused by 135 tors of tropical diseases 190 moths. Lepidoptera (moths and 136 associated with significant 191 d caterpillars) 137 morbidity and mortality (eg, Injuries from ants or aquatic insects can 192 Key points 138 mosquitoes, sand flies, tsetse result from stings and/or bites. 193 d Contact with Lonomia 139 flies, etc), other insects cause d The venom of bees and wasps may 194 caterpillars can cause a 140 cutaneous injury via venom, produce anaphylactic shock and death. 195 potentially fatal hemor- 141 vesicants, and allergens. This 196 d Cantharidin or paederin from beetles can rhagic syndrome 142 review covers tropical insects 197 cause vesicular dermatitis. d Pararama, caused by 143 causing injury not involving 198 d contact with Premolis 144 an infectious agent. The most common manifestation of 199 larvae, can cause peri- 145 bedbug bites is severe pruritus. 200 articular fibrosis and 146 d Myiasis may occur from fly larvae feeding 201 CLASS INSECTA ankylosis 147 Among the insects, there on necrotic or living tissue, but New 202 148 are some orders which are World screwworm larvae burrow deeply Injuries caused by lepidop- 203 149 closely related to envenoma- into living tissue, causing more severe terans are called erucism and 204 150 tion and various human dis- injury. lepidopterism.5-7 Although 205 151 206 eases, such as the orders d Tungiasis is characterized by pruritic envenomation by caterpillars 152 Lepidoptera (butterflies and papules and ulcers. (erucism) is very frequent, 207 153 moths), Hymenoptera (ants, they have only rarely been 208 154 bees and wasps), Coleoptera studied because of low re- 209 155 (beetles), Diptera (flies porting, which hinders a com- 210 156 and mosquitoes), Hemiptera (bugs), Dictyoptera plete understanding of the problem. It is not known 211 157 (cockroaches, praying mantis, and termites), exactly how the caterpillar venom acts. Pathology is 212 158 213 159 214 From the Departments of Dermatology at the Universidade Funding sources: None. 160 Estadual Paulista,a Viral Brazil Hospital, Instituto Butantan and Accepted for publication April 12, 2012. 215 161 Marine School of Biology, Botucatu; Fundacao de Medicina Reprint requests: Stephen K. Tyring, MD, PhD, Center for Clinical 216 162 Tropical do Amazonas,b Manaus; Universidade Federal do Studies, University of Texas Health Science Center, 451 N Texas 217 163 Estado do Rio de Janeiro and Policlinica Geral do Rio de Ave, Houston, TX 77598. E-mail: [email protected]. 218 c ddd 164 Janeiro, Immunology Section, Faculdade de Medicina, Uni- Published online . 219 versidade Federal do Rio de Janeiro, Brazil; and the University 0190-9622/$36.00 165 of Texas Health Science Center,d Houston, Texas. 220

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221 275 222 276 223 277 224 278 225 279 226 280 227 281 228 282 229 283 230 284 231 Fig 1. Lepidopterism. The moths of the Hylesia genus are 285 capable of causing injuries in humans through barbed 232 286 bristles released into the air. Photograph courtesy of Jo~ao 233 Luiz Costa Cardoso, MD. 287 288 234 289 235 290 236 291 237 292 238 293 239 294 240 295 241 296 242 297 243 Fig 3. Erucism. Erythema and mild edema in patients that 298 244 suffered injuries by Megalopigidae caterpillars. The pain is 299 245 always more important than the inflammation. Photograph 300 246 courtesy of Vidal Haddad Jr, MD. 301 247 Fig 2. Lepidopterism. Typical erythematous papules 302 248 caused by Hylesia moths on exposed areas in 2 children 303 249 that slept in an outdoor environment 1 day before the 304 observation and saw the moths attracted by a light. 250 305 Photograph courtesy of Jo~ao Luiz Costa Cardoso, MD. 251 306 252 attributed to fluids from the hemolymph and the 307 253 secretion of the spicules, with histamine being the 308 254 main component identified thus far. Forms of adult 309 255 moths can also cause dermatitis (lepidopterism). 310 256 Lepidopterism occurs through the bristles of the 311 257 Hylesia genus (Saturniidae family); under certain 312 258 conditions, this genus experiences population ex- 313 259 plosions in rural areas and during the rainy and Fig 4. Erucism. Superficial skin necrosis observed after 314 260 warmer months in tropical areas.8-11 Females in the contact with a Saturniidae caterpillar. Photograph courtesy 315 261 reproductive period approach light sources and of Vidal Haddad Jr, MD. 316 262 release ‘‘clouds’’ of bristles from their abdomens; 317 263 these can penetrate human skin and cause an irritat- reveals a foreign body reaction with granulomas. 318 264 ing dermatitis (Figs 1 and 2). There appears to be The use of oral antihistamines is indicated for the 319 265 toxins in the bristles,9,10 but the simple penetration of control of pruritus, and topical treatment with cold 320 266 the spikes seems to cause inflammatory reactions. compresses, baths, and corticosteroid creams is 321 267 The irritation is severe, manifested by erythematous recommended.10,11 322 268 papules, swelling, and itching just a few hours after Erucism (from the Greek erucae [larvae]) is the 323 269 contact. Occasionally, conjunctivitis, keratitis, and term used for envenomation caused by contact with 324 270 iritis can be observed, which undoubtedly are asso- larval forms of moths.5-7 The majority of problems 325 271 ciated with the popular belief that ‘‘the dust of the caused by lepidopterans start with inflammatory 326 272 wings of moths can blind a person.’’ Accompanied dermatologic manifestations of acute onset that oc- 327 273 by intense pruritus, they heal 7 to 14 days after cur by action of toxins.5,6 The manifestations occur 328 274 symptom onset. The histopathologic examination predominantly in the skin, depending on the 329

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330 385 331 386 332 387 333 388 334 389 335 390 336 391 337 392 338 393 339 394 340 395 341 396 342 397 343 398 344 399 345 400 346 401 347 402 348 403 349 404 350 405 Fig 5. Erucism. Megalopigidae caterpillars. Note the great 351 406 number of body setae or bristles. Photograph courtesy of Fig 7. Erucism. The caterpillars of the Lonomia genus 352 Vidal Haddad Jr, MD. 407 353 (Saturniidae family) are gregarious animals capable of 408 causing severe envenomation with hematologic compli- 354 409 cations and occasionally, the death of the victim. Photo- 355 graph courtesy of Vidal Haddad Jr, MD. 410 356 411 357 Megalopyge. Larvae of these genera have 2 types of 412 358 bristles: the true venomous bristles, which are smaller 413 359 and pointed and contain the basal venom glands, and 414 360 the longer bristles, which are colorful and harmless. 415 361 The caterpillars of the family Saturniidae have 416 362 ‘‘thorns’’ and pointed branches resembling small 417 363 pine trees, with venom glands at the apices (Fig 6). 418 364 They are colorful, with green shades, spots, and 419 365 stripes that vary in individual genera and species. 420 366 These colors often mimic the plants the caterpillars 421 367 inhabit. The important genera are: Automeris, 422 368 Dirphia, and Lonomia, the latter of which causes a 423 Fig 6. Erucism. Saturniidae caterpillars. The ‘‘pine trees’’ 369 potentially fatal hemorrhagic syndrome from contact 424 370 bristles are characteristic of this family. Photograph cour- 5 425 tesy of Vidal Haddad Jr, MD. with colonies of caterpillars in fruit trees. 371 Contact with Lonomia caterpillars (Fig 7) results in 426 372 intensity and extent of contact. There is initially local an intense fibrinolytic action similar to disseminated 427 373 pain, mild to moderate erythema, edema, and occa- intravascular coagulation, which causes major and 428 374 sional local pruritus (Fig 3). There are characteristic potentially fatal bleeding, with extremely low plasma 429 375 infarcted and painful regional lymph nodes. In the levels of fibrinogen, plasminogen, and other coagu- 430 376 first 24 hours, the lesions may progress to blistering lation factors. At the point of contact, the initial 431 377 and, more rarely, necrosis in the area of contact (Fig symptoms resemble those caused by other lepidop- 432 378 4). Injuries associated with erucism have intense and teran larvae, showing inflammatory phenomena. 433 379 prolonged pain as the primary symptom. The man- The presence of ecchymosis and suffusion indicates 434 380 ifestations regress in 24 to 48 hours.5,6 The main bleeding that is either local or systemic11,12 (Fig 8). 435 381 families of Lepidoptera that cause erucism are The differential diagnosis can be made by clinical 436 382 Megalopygidae, Arctiidae, and Saturniidae. history, agent identification, and observation of 437 383 The Megalopygidae have body setae with venom bleeding disorders. The treatment uses antilonomic 438 384 (Fig 5). The most important genera are Podalia and serum, which is present in liquid form.13,14 439

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440 495 441 496 442 497 443 498 444 499 445 500 446 501 447 502 448 503 449 504 450 505 451 506 452 Fig 10. Tocandira or bullet ant (Dinoponera spp). The 507 sting of this ant is very painful and causes systemic mani- 453 508 festations. Photograph courtesy of Vidal Haddad Jr, MD. 454 509 455 510 456 Fig 8. Erucism. Skin bleeding showing the coagulation inactivate total and C2 complement and promote a 511 457 disorders caused by envenomation after contact with chronic inflammation with granulomas (foreign 512 458 Lonomia catterpillars. Photograph courtesy of Jo~ao Luiz body reaction) in deep tissues (synovial membrane, 513 459 Costa Cardoso, MD. cartilage, and bone). The first contact does not 514 460 provoke sequelae; the process occurs after repeated 515 461 injury, suggesting an immunologic action for its 516 462 development.4 517 463 The diagnosis of erucism is simple when the 518 464 victims bring in the responsible animal. With the 519 465 exception of certain caterpillar types (eg, Lonomia 520 466 and Premolis), the envenomation has a good 521 467 prognosis and the manifestations fade in 2 to 3 522 468 days without major complications or sequelae. The 523 469 therapy of choice for envenomation by caterpillars 524 470 is local blockade with 2% lidocaine. Because the 525 471 injuries usually occur on the upper limbs, local 526 472 anesthesia easily controls the symptoms.5,6 In some 527 473 refractory cases, successive applications of anes- 528 474 thetic are necessary. As an additional measure, the 529 site can be washed, and compresses applied with 475 Fig 9. Pararama. Above: Premolis semirufa, the pararama 530 476 cold water and topical steroids with oral antihista- 531 caterpillar near to a rubber bowl in a sap tree. The bristles 5-7 477 of this larvae causes severe inflammation and ankylosis in mines, which reduce inflammation but not pain. 532 478 the fingers of the hands of workers of the sap tree (right). Envenomation by Lonomia requires hospitaliza- 533 479 Note the severe alterations in the radiographic examina- tion, and there is a serum antivenom produced at 534 480 tion. Photograph courtesy of Ronaldo Monteiro Costa, MD. the Butantan Institute in S~ao Paulo, Brazil. 535 481 Unexplained bleeding after contact with caterpil- 536 482 Pararama is a disease that is caused by the larvae lars guides the diagnosis, and the cases can be 537 483 of the Premolis species (Premolis semirufa is the found in Central and South America. Pararama 538 484 most often identified species); these larvae live in arthritis is a sequela progressing to total disability 539 485 rubber trees and are seen only in the Amazon region of the joints of the hand, and little can be done for 540 486 (Fig 9). The caterpillars’ venomous bristles penetrate the victim. 541 487 into the hands of victims who collect bowls of tree 542 488 sap, causing initial manifestations that do not differ Hymenoptera (ants and bees) 543 489 from those caused by other venomous caterpillars. In Key points 544 490 some individuals, the swelling persists after 2 or 3 d Bullet ants (Paraponera species) have the 545 491 days, and there is a progressive periarticular fibrosis most painful sting of any member of the 546 492 that leads to ankylosis and a loss of function of Hymenoptera order 547 493 articulation.15,16 The likely mechanism for the fibro- d Fire ants can cause injury simultaneously 548 494 sis and ankylosis is the presence of toxins that from bites and stings 549

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550 605 551 606 552 607 553 608 554 609 555 610 556 611 557 612 558 613 559 614 560 615 561 616 562 Fig 11. Pseudomyrmex ants or ‘‘novice’s ants’’ (Triplaris Fig 12. Red fire ant (Solenopsis invicta). This vicious ant 617 spp). These ants live naturally in trees, and their stings attacks anything that comes near the anthill with painful 563 618 cause intense pain and moderate local inflammation. stings. Photograph courtesy of Vidal Haddad Jr, MD. 564 Photograph courtesy of Vidal Haddad Jr, MD. 619 565 cutting ants or sauvas (Atta) do not contain venom, 620 566 d A massive number of bee stings can result in but occasionally can cut or lacerate human skin with 621 567 multiple organ failure because the venom is their jaws. A curious fact is that some indigenous 622 568 rich in phospholipases tribes use sauvas ants (which retains the reflexes of 623 569 Ants. Ants from the order Hymenoptera belong the mandibles even after the head is separated from 624 570 to the family Formicoidea. Injuries caused by stings the body) to approximate the edges of wounds, as 625 571 or bites of ants are part of everyday life, especially for ‘‘natural’’ sutures.17,18 626 572 the inhabitants of rural areas. There are 3 subfamilies Pseudomyrmex ants can attack humans that touch 627 573 of medical importance.17,18 the ‘‘novice’s tree’’ (Triplaris spp); these ants live 628 574 The subfamily Ponerinae includes the important naturally in these trees, and their stings cause intense 629 575 genus Paraponera19 and their close relatives, the pain and discrete to moderate local inflammation 630 576 Dinoponera. These ants may reach several centime- (Fig 11). The problem is common in some South 631 577 ters in length, have dark coloration, and live either American regions and can be prevented by the 632 578 alone or in pairs in rotting wood and fallen logs, etc identification and avoidance of the trees.21 633 579 (Fig 10). They are found in South and Central The subfamily Myrmicinae ants include the 634 580 America. They are commonly called bullet ants, Solenopsis genus, the lavapes or fire ants.17,18 The 635 581 tocandiras, Cape Verdean, or 24-hour ants; the latter black fire ant (Solenopsis richteri) comes from the 636 582 term is probably associated with the intense and plains of Rio Grande do Sul State (Brazil), Argentina, 637 583 prolonged pain caused by the sting. Ponerinae ants and Uruguay, while the red fire ant (Solenopsis 638 584 inject venom through a stinger attached to an ab- invicta; Fig 12) originated in the Brazilian Pantanal 639 585 dominal venom gland.17-19 The pain associated with (a vast flooded area in the midwest of Brazil) but 640 586 the bullet ant’s sting is reported to be greater than today is widespread throughout the southeast of 641 587 that of any other member of the Hymenoptera order. Brazil and, when accidentally introduced in 642 588 The pain is rated 41 on the Schmidt Sting Pain Index. Louisiana and Alabama, colonized more than half 643 589 Poneratoxin is a paralyzing neurotoxin isolated from of the United States in fewer than 30 years.17,18 These 644 590 the venom that affects voltage-dependent sodium ants are carnivorous, preying on insects, eggs, young 645 591 ion channels and blocks synaptic transmission.20 birds, and small mammals. Moreover, they have the 646 592 Otherwise, the venom is a poorly studied protein potential to cause envenomation and allergic 647 593 mix that is used by Amazon Indians for control of reactions. 648 594 rheumatic pains and also used in rituals of some Fire ants are not only a major pest to humans in 649 595 Indian tribes in the Amazon, who place their hands the southern United States, they are moving north- 650 596 into a container full of ants to test themselves in the ward, possibly because of global warming. They are 651 597 face of intense pain. also a major economic problem both because of 652 598 In subfamily Dorilinea, the Eciton genus (army damage to livestock and to crops. Fire ants are 653 599 ants) can cause human injuries. They travel through notoriously difficult to eradicate, even self- 654 600 the jungles of the Amazon in thousands of individ- assembling into waterproof rafts to survive floods.22 655 601 uals, preying and eating small live animals.17,18 The On the other hand, fire ants are not known to carry 656 602 stings of Eciton ants are moderately painful and there disease, and the do consume large amounts of ticks, 657 603 are no studies about the characteristics of the enven- fleas, and other arthropods that carry infectious 658 604 omation or the composition of the venom. Leaf- microorganisms. 659

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660 715 661 716 662 717 663 718 664 719 665 720 666 721 667 722 668 723 669 724 670 725 671 726 672 727 673 728 674 729 675 730 676 731 677 732 678 733 679 734 680 735 681 736 682 737 683 Fig 13. Red fire ant. A red fire ant stinging a human and the sequence of the action of the 738 684 venom (an initial urticariform papule and a sterile pustule 24 hours after the sting). Photograph 739 685 courtesy of Vidal Haddad Jr, MD. 740 686 Ants of the Solenopsis genus have venom that 741 687 differs from most animal venoms in that it is com- 742 688 prised of oily alkaloids. Its major fraction is solenop- 743 689 sin A, which has a cytotoxic effect that can 744 690 degranulate mast cells. An interesting fact is that 745 691 10% of the venom inoculated by the ants is a 746 692 nontoxic protein that can cause allergic reactions of 747 693 varying degrees. 748 694 The formation of a sterile pustule within 24 hours 749 695 after the bite is associated with the sting of S invicta. 750 696 The mechanism of the sting of these ants is charac- 751 697 teristic: the ant attaches to the skin with its jaws and 752 698 rotates on its axis, applying a dozen stings, if not 753 699 removed.23 Fire ants cause injury simultaneously 754 700 from both bites and stings. The burning pain is the 755 701 main initial symptom of the injury. An urticarial, 756 702 erythematous, extremely pruritic papule immedi- 757 703 Fig 14. Apiidae. A group of Africanized bees (Apis spp). 758 ately forms at the point of the sting, which in about Photograph courtesy of Vidal Haddad Jr, MD. 704 24 hours will lead to a sterile pustule caused by the 759 705 migration of neutrophils (Fig 13). Envenomation The stings of ants can be aggravated by the 760 706 with multiple stings causes important pustular man- development of secondary infection at the site and 761 707 ifestations that can be confused with other skin allergic reactions of varying severity. There are no 762 708 diseases.17,23 These injuries occur with small chil- laboratory tests used in the diagnosis of envenoma- 763 709 dren or intoxicated individuals. In addition to the tion. Desensitizations against allergic manifestations 764 710 painful symptoms common to all stings, the immu- caused by red fire ants (S invicta) are available in the 765 711 nogenic capacity of protein fractions and nontoxic United States, with controversial results. 766 712 venom of the fire ants may cause allergic reactions of Ant stings should be treated with the administra- 767 713 varying degrees, some extremely serious, including tion of antihistamines (dexchlorpheniramine, pref- 768 714 anaphylactic shock.23,24 erably), cold compresses to control pain, and topical 769

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770 825 771 826 772 827 773 828 774 829 775 830 776 831 777 832 778 833 779 834 780 835 781 836 782 Fig 15. Apiidae. Fatal multiple attack by Africanized bees. 837 783 Note the stingers on the skin and dead bees with the part 838 of the digestive tube linked to the stinger. Photograph 784 839 courtesy of Manoel Francisco Campos Neto. 785 840 786 841 787 corticosteroids. Massive envenomation can be med- 842 788 icated with oral corticosteroids. Prednisone can be 843 789 initiated at a dose of 30 mg for 1 to 3 days, tapering 844 790 to 10 mg per day until the withdrawal of the Fig 16. Paederus beetles. Vesicant beetles of the Paederus 845 791 drug. Patients with a history of allergy to stinging genus (top) and Epicauta genus (bottom). These beetles 846 792 ants should have the same care as those allergic are cosmopolitan, and typical injuries in humans can be 847 793 to bee stings, and if possible should have a kit observed around the world, especially in hot weather 848 794 available with adrenaline, antihistamines, and regions. Photograph courtesy of Vidal Haddad Jr, MD. 849 795 corticosteroids.17,18 850 796 Bees. Bees are social hymenoptera of the Apiidae 851 797 family that live in colonies with varying degrees of The treatment of a few bee stings involves anti- 852 798 functions between individuals (Fig 14). When dis- histamines and corticosteroid creams. Multiple stings 853 799 turbed, they attack through a stinger in the abdomen, are treated symptomatically. In attacks with multiple 854 800 similar to ants, which is detached from the bee with stings, it is essential to carefully extract the stingers 855 801 part of the digestive system, killing the insect (Fig with the venom glands still not emptied, which 856 802 modifies the prognosis of the envenomation by 857 15). The stingers can be seen in the skin of the victim, 4,25 803 and early extraction with clamps decreases the reducing the amount of injected venom ; other- 858 804 amount of the venom injected and improves the wise, the stingers will remain in the skin and, when 859 805 prognosis of the envenomation. Bees attack alone or pressed, will discharge their contents, increasing the 860 806 in groups. In the latter situation, they cause poten- envenomation. Anaphylactic shock should be trea- 861 807 tially fatal injuries. The venom provokes local in- ted with corticosteroid injections, promethazine, and 862 808 flammatory reactions (pain, edema, erythema, millesimal adrenalin in emergency rooms because of 863 809 papules, or plaques), toxic reactions (after multiple the high risk of death. 864 810 865 stings, with potential kidney failure, heart failure, or Coleoptera (beetles) 811 death), and allergic reactions, which can be serious, 866 812 Key points 867 such as anaphylactic shock. Massive attacks became d 813 Cantharidin in ‘‘blister’’ beetles cause vesi- 868 common after the hybridization of African and cles and bullae by activation of neutral ser- 814 European bees, generating an aggressive hybrid 869 815 ine proteases, which cause degeneration of 870 that has spread across America from a fugitive colony desmosomes 816 in Brazil nearly 40 years ago. Bees and wasps can 871 d Paederin in the Paederus beetle is an amide 817 cause serious injuries by allergic phenomena. A high 872 818 with vesicant action which blocks mitosis by 873 risk of death can result from multiple organ failure as acting on cellular DNA 819 a result of venom, rich in phospholipases, after a 874 820 massive number of stings.4,25 Vesicant beetles are cosmopolitan and cause 875 821 The Meloponidae family ( jataıs or irapoas~ ) are injuries in every continent except the polar regions. 876 822 stingless bees that can become stuck in the hair of the Most of these insects belong to the Paederus genus1-4 877 823 victims when they feel threatened. In extreme cases, (Fig 16). In Brazil, the term poto is used for 2 different 878 824 they can only be removed by cutting the hair.26 beetles, both causing vesicular dermatitis, also called 879

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880 linear dermatitis. ‘‘Poto-pepper,’’ ‘‘Poto-large,’’ or 935 881 ‘‘donkeys’’ are beetles that belong to the Meloidea 936 882 family, measuring 1.5 to 3.0 inches in size, with 2 937 883 genera associated with injuries: Lytta and Epicauta. 938 884 Both genera include beetles that feed on leaves of 939 885 crops, such as tomatoes and potatoes, making their 940 886 interaction with humans likely. One substance pro- 941 887 duced by these animals is cantharidin, a potent skin 942 888 and mucous irritant.3 943 889 Cantharidin is a vesicant that comes from more 944 890 than 1,500 species of ‘‘blister’’ beetles. It is absorbed 945 891 into the lipid component of keratinocyte mem- 946 892 branes, where it actives neutral serine proteases, 947 893 leading to the degeneration of desmosomes and 948 894 resulting in vesicles and bullae.27 Cantharidin is also 949 895 the primary ingredient of ‘‘Spanish fly,’’ a purported 950 896 aphrodisiac that is made by grinding dried ‘‘blister’’ 951 897 beetles. The so-called aphrodisiac effects of canthar- 952 898 idin are related to its ability to produce irritation of 953 899 the genital track, mimicking arousal. 954 900 Poto and ‘‘wildfire’’ are names given to the 955 901 beetles of the Paederus genus, Staphylinidae family; 956 902 they are easy to recognize from the elytra (shells 957 903 that protect the wings) overlying the anterior por- 958 904 tion of the dorsum of the abdomen. The cosmo- 959 905 politan Paederus can fly, has nocturnal habits, and 960 Fig 17. Paederus beetles. The classic herpetiform lesions 906 is attracted to artificial light sources, invading 961 907 caused by vesicant beetles (in this case, Paederus spp) are 962 homes and causing linear dermatitis. They feed localized to exposed parts of the body (top). The photo- 908 963 on plant debris and are quite common in crops of graph on the bottom shows a typical pattern (the ‘‘kiss 909 maize and beans. The life cycle of the beetle is long, sign’’) caused by the contact with the venom in a skin 964 910 passing through 7 intermediate larval stages before flexure. Photograph courtesy of Vidal Haddad Jr, MD. 965 911 the adult form, multiplying at the rate of 1 cycle per 966 912 year.1 More than 600 species of Paederus are known 967 913 The Paederus beetle produces paederin, a crys- throughout the tropical and temperate regions of the 968 914 talline and powerful caustic amide with vesicant globe. About 4% of the species cataloged as 969 915 action, soluble in water and alcohol, which can block Paederus are recognized as causing linear dermati- 970 916 mitosis by acting on cellular DNA.4 Paederin seems tis.28-31 971 917 to have some differences compared to cantharidin, The toxin of Paederus fuscipes was characterized 972 918 causing more intense erythema and smaller vesicles as paederin, which differs chemically from canthar- 973 919 that converge and form blisters. Symptoms (burning idin.4,28 The dried extracts obtained from animals 974 920 and itching) are more intense in injuries secondary to maintained their activity for about 8 years.25 975 921 Paederus injuries because human contact with these Injuries caused by vesicant beetles occurs in hot 976 922 types of secretions is generally not serious, which and rainy months.1,2,31 The beetle is attracted to 977 923 contributes to the relative lack of published literature artificial light sources. The discharge of secretion 978 924 about this disease. occurs when the victim tries to ward off the animal 979 925 First described in Indonesia in the summer of and presses it against the skin, usually on the neck, 980 926 1891, potos were already known to the Chinese for face, or limbs, but any exposed areas may have 981 927 1,200 years and already used in therapy, as shown in lesions.32 According to the extent and the number of 982 928 a manuscript from China dating from 739 AD: the the contacts, the injury can be classified as mild, 983 929 insect has powerful venom, and when it touches the moderate, or severe. In the latter case, there are 984 930 skin, it causes swelling. The venom causes the skin to systemic manifestations, such as nausea, vomiting, 985 931 peel and (can) completely remove tattoo marks. It and fever.4 986 932 can be used as a caustic against blisters, nasal polyps, After the discharge of the substance, the skin 987 933 or scurvy. The Paederus beetle is approximately 1 cm shows erythema for a day or two, accompanied by 988 934 in length.28 pruritus and burning. After this period, vesicles 989

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990 1045 991 1046 992 1047 993 1048 994 1049 995 1050 996 1051 997 1052 998 1053 999 1054 1000 1055 1001 1056 1002 Fig 18. Pentatomidae. The stink bug of the Pentatomidae 1057 family recently was described as a cause of skin lesions in 1003 1058 humans. Photograph courtesy of Vidal Haddad Jr, MD. 1004 1059 1005 1060 1006 1061 1007 appear (small when the injury is caused by Paederus 1062 1008 and large when the agent is Epicauta or Lytta), which 1063 1009 evolve to the formation of sterile pustules, ulcera- 1064 1010 tions, and crusts (Fig 17). The lesions resolve in 1065 1011 about a week, leaving residual erythematous or 28 Fig 19. Pentatomidae. Inflammation caused by a sting 1066 1012 hyperchromic macules. The lesions are elongated 1067 or linear because of the act of rubbing the insect bug in a human. The lesions are similar to those caused by 1013 vesicant beetles. Photograph courtesy of Vidal Haddad Jr, 1068 against the skin and should be differentiated from 1014 MD. 1069 1015 contact dermatitis, phytophotodermatitis, varicella 1070 zoster, herpes simplex, pemphigus, and injuries 1016 4 1071 1017 caused by caterpillars. 1072 1018 Lesions should be immediately and intensively 1073 1019 washed with clean water and soap. Some authors 1074 1020 advocate the use of tincture of iodine in early lesions, 1075 1021 because this would act as a solvent. Vesicles, crusts, 1076 1022 and pustules should be treated with potassium 1077 1023 permanganate compresses (1 tablet in 4 L of water) 1078 1024 twice a day and corticosteroid creams. If there is 1079 1025 secondary infection, it is necessary to use topical or 1080 1026 systemic antibiotics. 1081 1027 1082 1028 Hemiptera (true bugs) Fig 20. Belostomatidae. Giant water bugs of the Belosto- 1083 1029 Key points matidae family are responsible for painful stings in hu- 1084 d 1030 Contact with stink bugs can cause burning mans. Photograph courtesy of Vidal Haddad Jr, MD. 1085 1031 and pruritus 1086 d 1032 The painful bite of giant water bugs causes 1087 tissue injury by lysophospholipids in the recently related to vesicular and erythematous pla- 1033 ques in the same regions affected by vesicant beetles, 1088 1034 bug’s saliva, which cause paralysis in the 33 1089 neuromuscular junction of the prey which are accompanied by burning and pruritus 1035 (Fig 19). The differential diagnosis can be difficult. 1090 d Recent increases in bedbugs may be related 1036 The treatment is similar to that used after contact with 1091 1037 to their resistance to insecticides and elimi- 1092 nation of their predators Paederus or cantharidin, although there is no infor- 1038 mation on the pharmacologic properties of sub- 1093 1039 Suborder Heteroptera stances secreted by the Pentatomidae. 1094 1040 Pentatomidae family. Similar to the vesicant Belastomatidae family. Venomous aquatic in- 1095 1041 beetles, some insects of the order Hemiptera (family sects are rare, but the arthropods of the 1096 1042 Pentatomidae) can cause serious irritation to human Belostomatidae family can cause painful stings in 1097 1043 skin (Fig 18). These insects are popularly known as humans.34-36 The Belostomatidae or giant water bugs 1098 1044 marias-fedidas (‘‘stink Mary’’) and they have been are cosmopolitan insects that live in tropical, 1099

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1100 1155 1101 1156 1102 1157 1103 1158 1104 1159 1105 1160 1106 1161 1107 1162 1108 1163 1109 1164 1110 1165 1111 1166 1112 Fig 21. Belostomatidae. Erythematous papule at the point 1167 of a bite of a giant water bug. The skin signs were not 1113 1168 proportional to the severe pain. Photograph courtesy of 1114 Vidal Haddad Jr, MD. 1169 1115 1170 1116 subtropical, and temperate areas (Fig 20). The giant 1171 1117 water bugs are classified in 2 main genera 1172 1118 (Lethocerus and Belostoma).35 They are found in 1173 1119 freshwater habitats, such as ponds, lakes, and rivers, 1174 1120 and are associated with an unpleasant sting that has 1175 1121 led to the name of ‘‘toe biters’’ to describe these Fig 22. Cimex spp. Bedbugs are a curse resurrected in 1176 1122 insects that may defensively attack the foot of a modern times. Note the blood in the abdomen of the 1177 1123 wader or hurt someone who picks them up.35,36 parasite and lesions in the distribution of ‘‘breakfast, lunch, 1178 1124 They can often be observed feeding upon tadpoles, and dinner.’’ Photographs courtesy of Vidal Haddad Jr, 1179 ~ 1125 fish, and even animals as large as ducklings. They MD, and Joao Luiz Costa Cardoso, MD. 1180 1126 breathe in the water with a siphon tube projecting 1181 1127 from the back of their abdomen and can be found 1182 1128 hanging head down at the surface of the water, but 1183 1129 are also highly capable swimmers.2 These Hemiptera 1184 1130 have popular names in Brazil, as water cockroach, 1185 1131 water scorpion, arauemboia , bota-mesa, and finger 1186 1132 stinger. 1187 1133 Giant water bugs can reach large diameters, as 1188 1134 seen in the genus Lethocerus, where insects are 1189 1135 recorded at sizes up to 10 cm. They have a short 1190 1136 stout beak that is used to pierce their prey and 1191 1137 present toxic saliva. The main species of the genus 1192 1138 Lethocerus in Brazil are L delpontei, L grandis, and Fig 23. Cimex spp. The bites from bedbugs are not 1193 1139 L maximus.35,36 accompanied by severe manifestations in nonsensitized 1194 1140 The saliva of these insects is a mix of enzymes persons, but they can cause notable erythema, edema, and 1195 1141 capable of liquefying the tissues of the prey, but itching in those persons allergic to the bites (especially 1196 1142 there are also other toxic effects. The toxicity of the atopic individuals). 1197 1143 saliva of these animals was studied by Picado,37 who 1198 1144 reported ‘‘increased clotting of blood in men and insects are parasites, and there have been reports of 1199 1145 animals, hemolysis similar to that associated with infestation in humans since the time of ancient 1200 1146 venom of snakes in rabbits but not in humans.’’ Rome. They are hematophagous and have 2 blades 1201 1147 Recently, there was demonstration of the presence of in the proboscis: one to inject an anesthetic and the 1202 1148 lysophospholipids in the saliva of the species other to suck blood1,2 (Fig 22). Like ticks, the 1203 1149 Belostoma anurum that can cause paralysis in the presence of inflammatory reactions at the point of 1204 1150 neuromuscular junction of their prey.38 These insects the bites can cause significant discomfort to the 1205 1151 are capable of producing painful lesions in humans victim (Fig 23). Bedbugs are found in overcrowded 1206 1152 and possibly of carrying infections39 (Fig 21). areas of towns and cities, and their presence has 1207 1153 Cimicidae family. Recently, an old foe has traditionally had a deep relationship with low stan- 1208 1154 returned with strength: the bites of bedbugs. These dards of sanitation, but bedbugs are now reported in 1209

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1210 ‘‘upscale’’ homes and hotels. One possible reason for 1265 1211 the increase in bedbugs may be the better control of 1266 1212 cockroaches, which prey on them. 1267 1213 Bedbugs were common parasites in several coun- 1268 1214 tries until the deployment of dichlorodiphenyltri- 1269 1215 chloroethane and pyrethrum insecticides in the 1270 1216 1940s. Pesticides have greatly reduced the presence 1271 1217 of these arthropods; for a long period, they were not 1272 1218 a problem for domestic environments in the 1273 1219 Americas. In recent years, a combination of factors 1274 1220 caused bedbugs to return—the most potent insecti- 1275 1221 cides have been abandoned because of the delete- 1276 Fig 24. Myiasis of the scalp. Dermatobia hominis. 1222 rious effects to the environment, the presence of 1277 1223 bugs in some poor countries has increased, and spp.41 Lesions in sensitized individuals may simulate 1278 1224 international travel has become more common. infections and envenomation. The eradication and 1279 1225 Other factors include recent resistance to pyrethroids prevention of bedbugs can be tried by the removal of 1280 1226 and dichlorodiphenyltrichloroethane, the ability of infested furniture, including those in transport vehi- 1281 1227 the bedbugs to survive up to a year without food, and cles, and exercising caution in the purchase of 1282 1228 the transportation of these bugs in luggage, resulting second-hand furniture and old building materials. 1283 1229 in numerous reports of bedbugs in European Bedbug pesticide resistance appears to be a great 1284 1230 and American countries (especially in hotels); ther- problem. This resistance includes deltamethrin and 1285 1231 apeutic and preventive measures should be familiar bait insecticides for cockroaches.42 The most effec- 1286 1232 to dermatologists. tive insecticides are pyrethroids, dichlorvos, and 1287 1233 The most common species in Europe, the malathion.42 While no infectious diseases have 1288 1234 Americas, and Australia is Cimex lectularius (the been proven to be transmitted by bedbugs, more 1289 1235 common bedbug) and Cimex hemipteras, which is than 100 illnesses have been reported with bedbug- 1290 40 1236 present in all warmer regions of earth. Bedbugs live related insecticide use, including 1 fatality.43 Almost 1291 1237 in groups (nymphs, eggs, and adults among blood 90% of the cases, including the fatality, were associ- 1292 1238 droppings, which present a black coloration) in ated with the use of pyrethroids and/or pyrethrins. 1293 1239 cracks in walls or in wood (in bed frames, for 1294 1240 example), behind woodwork on the wall, ventila- 1295 Diptera (true flies) 1241 tors, and in furniture of all types. They feed by 1296 Key points 1242 sucking the blood of victims during the night, when 1297 d Botflies indirectly cause myiasis by attaching 1243 they are attracted by CO and heat, moving with 1298 2 its eggs to a mosquito or muscoid fly vector 1244 great rapidity.40 One interesting fact is the strong and 1299 which then transfers the eggs or larvae to the 1245 offensive odor caused by 2 or 3 glands. The odor is 1300 host 1246 capable of repelling predators of the hemiptera. 1301 d The New World screwworm fly feeds on 1247 Bedbugs bite exposed areas of the victim (espe- 1302 healthy tissue of livestock and humans and 1248 cially the head, neck, and arms) and cause erythem- 1303 burrows (ie, screws) deeply into tissue 1249 atous and pruritic papules and macules (rarely 1304 1250 blisters) that can become infected after scratching. Whereas flies are a nuisance throughout most of 1305 1251 The skin lesions show similarity with injuries caused the world because of their bites (eg, deer flies), 1306 1252 by other arthropods, such as fleas. There is a typical others carry infectious diseases (black flies carry 1307 1253 distribution of the bites, seen with sequential lesions onchocerciasis; tsetse flies carry trypanosomiasis). 1308 1254 (‘‘breakfast, lunch, and dinner’’). The severity of the Most fly larvae (maggots) provide a useful function 1309 1255 lesions is determined by the degree of sensitivity of in nature by eating decaying matter, and they can 1310 1256 the victim to the hemiptera.40 even be used therapeutically. Some maggots, how- 1311 1257 When necessary, treatment includes antihista- ever, feed on living tissue. The general term for 1312 1258 mines and topical steroids. Nonsensitized individ- infestation of maggots feeding on the host’s necrotic 1313 1259 uals do not develop significant lesions or symptoms. or living tissue is myiasis (Fig 24). This problem is 1314 1260 There is the possibility of secondary bacterial infec- commonly seen in tropical countries and in travelers 1315 1261 tions; therefore, it is important to apply topical returning from tropical parts of the world. Botflies, 1316 1262 antibiotics. There is no proven disease transmitted blowflies, and fleshflies are the 3 main families 1317 1263 by the bite of bedbugs, but numerous candidate causing myiasis in livestock and occasionally in 1318 1264 pathogens can potentially be transmitted by Cimex humans. 1319

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1320 1375 1321 1376 1322 1377 1323 1378 1324 1379 1325 1380 1326 1381 1327 1382 1328 1383 1329 1384 1330 Fig 25. Screwworm larvae. Cochliomyia hominivorax 1385 1331 feeding on viable human tissue of the pelvis. Photograph 1386 1332 courtesy of Michael Mays. Fig 26. Tungiasis of the foot (Tunga penetrans). 1387 1333 The female human botfly, Dermatobia hominis, 1388 1334 captures one of more than 40 species of mosquitoes flea followed by antibiotic therapy for sec- 1389 1335 or muscoid flies and attaches its eggs to the vector’s ondary infections 1390 1336 body. After releasing the vector, the eggs hatch while 1391 Although fleas are vectors of numerous infectious 1337 the mosquito is feeding on the host and the larvae 1392 diseases, their most commonly recognized nonin- 1338 use the bite entry site. Alternatively, the eggs simply 1393 fectious injury is their pruritic bite. Penetration of the 1339 drop off the muscoid fly when it lands on the skin. 1394 skin by the female ectoparasitic Tunga penetrans 1340 Cutaneous myiasis usually presents as slowly grow- 1395 flea, however, can cause severe pruritus, pain, 1341 ing nodules that resemble furuncles or as ulcers, but 1396 inflammation, and swelling. Tungiasis, also known 1342 myiasis may also be nasal, aural, or ophthalmic. 1397 as nigua, pio, bicho de pie, and pique, is character- 1343 Treatment of myiasis includes the use of forceps, 1398 ized by a black dot at the center of an erythematous 1344 excision, or occlusion/suffocation approaches (eg, 1399 papule surrounded by a white halo (Fig 26). 1345 tape, nail polish, glue, or petroleum jelly). An alter- 1400 Desquamation of the skin is seen after expansion 1346 native method of convincing the botfly to exit the 1401 of the flea during feeding. Without treatment, sec- 1347 skin is to apply an irritant such as chewing tobacco, 1402 ondary infections, tetanus, and gangrene can de- 1348 snuff, or camphor oil. 1403 velop. T penetrans is the world’s smallest flea and is 1349 The larvae of the New World screwworm fly, 1404 known as the chigoe flea, jigger, nigua, and sand 1350 Cochliomyia hominivorax, feed on the healthy tis- 1405 flea, and is found in Central and South America, the 1351 sue of livestock and occasionally humans. 1406 Caribbean, Africa, and India. Treatment usually 1352 Screwworm females lay eggs in the exposed flesh 1407 involves extraction of the flea followed by antibiotic 1353 (eg, wounds). When the larvae hatch, they burrow 1408 therapy for secondary infections. Alternatively, cry- 1354 into surrounding tissue as they feed (Fig 25). If the 1409 otherapy or occlusion/suffocation can be used. 1355 wound is disturbed, the larvae burrow or ‘‘screw’’ 1410 Many tropical insects cause morbidity and mor- 1356 deeper into the tissue, which is the source of the fly’s 1411 tality in their role as vectors for infectious diseases. 1357 name. The larvae are capable of causing severe tissue 1412 Other tropical insects, however, cause injury via the 1358 damage, including death of the host. Screwworms 1413 release of venom, vesicants, irritants, or allergens, 1359 were officially eradicated from the United States in 1414 etc. It is important for dermatologists to be familiar 1360 1982, using the sterile insect technique, but the 1415 with these insects and the injuries they cause in order 1361 problem continues in Central and South America 1416 to initiate proper therapy and to advise the patient on 1362 and the Caribbean. Treatment of screwworm larvae 1417 effective prevention. 1363 infestation includes manually removing the maggots, 1418 1364 debriding the necrotic tissue, and prescribing anti- 1419 1365 biotic therapy for secondary infections. REFERENCES 1420 1366 1. Alexander JD. Arthropods and human skin. London (UK): 1421 1367 Springer Verlag; 1984. 1422 Siphonaptera (fleas) 2. Goddard J. Arthropods of medical importance. Boca Raton 1368 Key points (FL): CRC Press; 1993. 1423 1369 d Tungiasis is associated with pruritus, pain, 3. Carrera M. Insetos de interesse medico e veterinario. Curitiba 1424 1370 inflammation, and swelling, and results (Brazil): Editora da Universidade do Parana; 1991. 1425 1371 from penetration of the skin by the Tunga 4. Cardoso JLC, Franc¸a FOS, Wen FH, Malaque CMS, Haddad V Jr. 1426 1372 Venomous animals in Brazil: biology, clinic and therapeutic [in 1427 penetrans flea Portuguese]. S~ao Paulo (Brazil): Editora Sarvier; 2009. 1373 d Treatment of tungiasis involves extraction, 5. Cardoso AEC, Haddad V Jr. Accidents caused by lepidopterans 1428 1374 cryotherapy, or occlusion/suffocation of the (moth larvae and adult): study on the epidemiological, clinical 1429

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1430 and therapeutic aspects [in Portuguese]. An Bras Dermatol 24. Conceic¸~ao LG, Haddad V Jr, Loures FH. Pustular dermatosis 1485 1431 2005;80:571-8. caused by fire ant (Solenopsis invicta) stings in a dog. Vet 1486 1432 6. Haddad V Jr, Cardoso JLC. Erucismo e lepidopterismo [in Dermatol 2006;17:453-5. 1487 1433 Portuguese]. In: Cardoso JLC, Franc¸a FOS, Weh FH, Malaque 25. Franc¸a FO, Benvenuti LA, Fan HW, Dos Santos DR, Hain SH, 1488 CMS, Haddad V Jr, editors. Venomous animals in Brazil: biology, Picchi-Martins FR, et al. Severe and fatal mass attacks by 1434 clinic and therapeutics. S~ao Paulo (Brazil): Editora Sarvier; 2009. ‘‘killer’’ bees (Africanized honey bees e Apis mellifera scutel- 1489 1435 7. Haddad V Jr. Identification of acute diseases caused by animals lata) in Brazil: clinicopathological studies with measurement of 1490 1436 and plants in wild environments: contribution to dermatologic serum venom concentrations. 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Location Query / Remark: Click on the Q link to find the query’s location in text in article Please insert your reply or correction at the corresponding line in the proof Q1 Please review the affiliations as shown on the proofs. Thank you. Q2 Please note this change from “Classes” to “orders.” Q3 Please note that throughout the manuscript, genus and species ranks are italicized, while ranks of family and above are presented without italics, per the AMA Style Guide. Q4 As edited, this sentence implies that Lonomia is the only genus that causes this syndrome. Are these changes correct, or do all 3 cause this syndrome? Q5 Please provide permission forms from all authors who have provided figures. Q6 Please confirm that patient consent forms have been received from the man in Fig 9. Q7 In Fig 15, please provide the highest academic degree obtained by Mr. Campos Neto, if possible. Thank you. Q8 In Fig 25, please provide the highest academic degree obtained by Mr. Mays, if possible. Q9 Author affiliations will appear differently in the print and online versions of your paper. The PDF shows how the affiliations will present following journal style, whereas the searchable online version will present as follows in order to provide complete unabridged affiliations. Please check the accuracy of the affiliation(s) of each author and make changes as appropriate. aDepartment of Dermatology at the Universidade Estadual Paulista, Viral Brazil Hospital, Instituto Butantan and Marine School of Biology, Botucatu, Brazil bDepartment of Dermatology, Fundacao de Medicina Tropical do Amazonas, Manaus, Brazil cUniversidade Federal do Estado do Rio de Janeiro and Policlinica Geral do Rio de Janeiro, Immunology Section, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil dUniversity of Texas Health Science Center, Houston, Texas Q10 Please note that the 2 versions of the article contained in this proof differ only in the CME Instructions. All changes made to the first version will be made to the second and, since the articles are identical, there is no need for an extensive review of the second version Q11 Please confirm that given names and surnames have been identified correctly.

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