Chapter 50 Arthropod Envenomation and Parasitism

Timothy B. Erickson, Armando Márquez, Jr.

For online-only figures, please go to www.expertconsult.com

The phylum Arthropoda contains about four-fifths of the known animals of the world, and insects are the largest group of arthropods. Insects are an important part of the biota of all terrestrial and freshwater environments that support life. More species of insects exist than of any other form of multicellular life, and they may well exceed all other land animals in biomass. Insects can use most animal and plant substances as food, and their feeding plays a vital role in recycling organic compounds. They compete with other organisms for the world’s food supplies but are themselves a major food source for many forms of life. They are essential for the pollination of many plants. Insect life cycles are diverse and often complex, involving developmental and sexual stages that are widely different in morphology and ways of life. Although sexual reproduction is the rule, parthenogenesis (unisexual reproduction) and pedogenesis (sexual development in the larval stage) occur. Some groups, such as ants, bees, and termites, have developed a high degree of social organization. During at least part of its life cycle, an insect’s body is divided into three distinct regions (head, thorax, and abdomen), with three pairs of legs attached to the thorax. Except for a few primitive or parasitic groups, most adult insects have wings.

The greatest direct medical importance of insects is associated with their feeding on human blood and tissue fluids. In doing so, they often inject salivary secretions. This is a highly effective method of transmitting pathogenic microorganisms; moreover, the secretions are often allergenic and sometimes toxic. Other insects may carry human pathogens passively on their feet or mouthparts or in their digestive tracts.

Venoms have evolved in several insect groups, and venomous insects may attack humans, sometimes with lethal results. Skin, hair, and secretions of insects may be irritant or allergenic, producing cutaneous and respiratory syndromes. Finally, insects can be highly annoying.

Hymenoptera (Bees, Wasps, and Ants)

By far the most important venomous insects are members of the order Hymenoptera, including bees, wasps, and ants (Figure 50-1). They vary in size from minute to large (up to 60 mm [2.4 inches] in body length). The abdomen and thorax are connected by a slender pedicle that may be quite long in certain wasps and ants. Bees and most wasps are winged as adults; ants are wingless, except for sexually mature adults during part of the life cycle. Mouthparts are adapted for chewing but in some species are modified for sucking. The life cycle includes egg, larval, and pupal stages before emergence of adults. Immature stages may be protected and provided with food by the adult. Both animal and plant foods are used. Many species are parasitic on other arthropods. All ants and many species of bees and wasps are social insects. Colonies range in size from a few dozen individuals to many thousands. In cold climates, most individuals die in autumn, leaving the fertilized females to winter over and found new colonies in the spring.

FIGURE 50-1 Representative venomous Hymenoptera. A, Hornet (Vespula maculata). B, Wasp (Chlorion ichneumerea). C, Yellowjacket (Vespula maculiforma). D, Honeybee (Apis mellifera). E, Fire ant (Solenopsis invicta). F, Bumblebee (Bombus species).

Bees

The honeybee (Apis mellifera) is one of the few domesticated insects and is maintained in hives in many countries (Figures 50-2 and 50-3). Numerous geographic races of the honeybee exist; the Italian bee (Apis mellifera ligustica), a common domestic strain of Europe, is also widely distributed in the United States. Feral honeybee colonies usually nest in hollow trees or crevices in rocks but may nest in the walls of occupied buildings.

FIGURE 50-2 Worker honeybee, Apis mellifera.

FIGURE 50-3 Stinger of a honeybee.

An event of considerable health and economic significance in the Americas was the introduction of an African race of the honeybee (Apis mellifera scutellata, also referred to as Apis mellifera adansoni). This race was introduced from Africa into Brazil because it was thought to be a more efficient honey producer in the tropics. It is characterized by large populations (one queen may lay tens of thousands of eggs), frequent swarming (6 to 12 swarms a year), nonstop flights of at least 20 km (12.4 miles), and a tendency toward mass attacks on humans after minimal provocation. As a result, these Africanized honeybees, also known as killer bees, are much more aggressive than are the typical Western Hymenoptera. They attack in swarms of hundreds and chase their victims much greater distances from the hive than does any other species.^155,¹⁸⁷

The first escapes from hives occurred in the state of São Paulo in 1957, and the “Brazilian killer bees,” or “Africanized bees,” have spread widely. These bees are actually hybrids between A. scutellata and European honeybee races.³⁷³ Cold climate seems to have stopped their southern spread in Argentina, but they have moved steadily northward at 322 to 482 km (200 to 300 miles) per year and in October 1990 reached the southern border of the United States.³⁷⁴ By mid-1991, 103 swarms had been captured in southern Texas. Populations are established in Arizona, New Mexico, and California.³²² The expanded distribution of Africanized honeybees from South America to the southwest United Sates in less than 50 years is considered one of the most spectacular biologic invasions yet documented.^284,³¹⁹ The resulting feral honeybee population of south Texas is now viewed as a hydrid swarm. Future populations may eventually be distributed as far east as North Carolina.³⁷¹ Several human deaths have occurred from multiple stings. Unless the bees acquire greater resistance to winter conditions, their range will be confined to the southern one-third of the United States and may also be restricted by scarcity of suitable flowers in the arid Southwest. Periods of the year characterized by high temperatures and low rainfall are conducive to the greatest activity of Africanized bees and a larger number of swarms, thus giving rise to increased contact with human populations.⁸⁶ The greatest impact of Africanized bees in the United States will probably be economic, related to decreased honey production and less effective pollination of crops. The bees also present a threat to human health. Africanized bee colonies are extremely sensitive to disturbance, respond faster in greater numbers, and are up to 10 times more active in stinging than are European bees. The quantity of venom per sting is slightly less in African bees; however, there is no significant biochemical or allergenic difference between the venoms.^237,^252,³²⁴ Africanized honeybees can overwhelm and kill even healthy nonallergic victims.³² About 50 simultaneous stings can cause systemic envenomation, and an estimated 500 are necessary to cause death by direct toxicity.¹⁷⁹ As few as 30 to 50 stings have proved fatal in small children.³⁹

About 350 fatal attacks have been documented worldwide, of which at least 70 occurred in Venezuela during 1977 and 1978. More than 300 bee attacks occurred in Mexico between 1987 and 1992, with 49 fatalities.²⁴⁹ A more recent account puts the fatalities at 190, with future estimates of 60 deaths per year.³²² Because Mexico and the southern United States have many feral and domestic honeybee populations, researchers thought that the aggressiveness of the African bees could be dampened by hybridization. Large numbers of male European bees were released to facilitate this, and African queens were replaced by European stock when possible. However, recent studies indicate that European bee populations are becoming rapidly Africanized with little reciprocal gene flow, as African females take over European hives.^156,^207,^336,³⁷⁵

Bumblebees (Bombus and related genera) are a largely holarctic group often found in quite cold environments. Increasing reactions to stings in Alaska may be related to the recent changing trends in climate.⁸⁵ Small colonies usually nest just under the surface of the ground, often in mammal burrows. Some species are aggressive if disturbed, although most have mild dispositions.²⁰⁸

Sweat bees (family Halictidae) are small bees of cosmopolitan distribution (Figure 50-4). They are attracted to sweaty skin and ingest perspiration. They nest in burrows, often in clay banks. Females sting if squeezed or trapped under clothing. The sting is not very painful, but anaphylactic reactions have been reported. The allergens are immunologically unrelated to those in other bee and wasp venoms.²⁷⁷

FIGURE 50-4 Sweat bee, family Halictidae.

(From http://www.encarta.msn.com.)

Wasps

Social wasps occur throughout most of the world but are recognized as a medical problem, chiefly in the United States and Europe. They often establish colonies close to human dwellings. Yellowjackets (Vespula species) may be more important than honeybees as a cause of human stings in the northern United States ²⁸⁶ (Figure 50-5). They make underground nests (Figure 50-6) in rotted-out tree stumps, cavities under stones, and mammal burrows. They are strongly attracted to garbage. Paper wasps (Polistes species) (Figure 50-7) suspend their nests in shaded places, often in shrubbery near houses or below eaves, gutters, or window frames. Old World hornets (Vespa species) and white-faced hornets (Dolchiovespula maculata) create large paper nests that may be plastered to buildings, but more typically hang from tree branches (Figures 50-8 and 50-9).

FIGURE 50-5 Yellowjacket, Vespula maculiforma.

FIGURE 50-6 Early yellowjacket nest.

FIGURE 50-7 Paper wasp, Polistes species.

FIGURE 50-8 White-faced hornet, Dolchiovespula maculata, largest of the common social wasps in the United States.

FIGURE 50-9 Typical nest of the white-faced hornet.

Solitary wasps are predators, feeding largely on other insects and spiders. Adults often carry the prey alive and paralyzed to the nest as food for the larvae. Some wasps excavate burrows, whereas others make mud nests that may be plastered on shaded walls of buildings or under bridges. Although many nests may be grouped together, the adult wasps have no social organization and make little effort to defend them. The cicada killers (Sphecius speciosus) (Figure 50-10) and tarantula hawks (Pepsis species) (Figure 50-11) are among the largest North American wasps. Velvet ants (family Mutillidae) are female wingless wasps that are nest parasites of other Hymenoptera (Figure 50-12). They are found in deserts and other dry and open habitats and can inflict a painful sting.

FIGURE 50-10 Cicada killer wasp, Sphecius speciosus.

(From http://www.ento.okstate.edu.)

FIGURE 50-11 Tarantula hawk, Pepsis species.

(Courtesy Mary Beth Stowe, McAllen, Tex.)

FIGURE 50-12 Velvet ant, family Mutillidae.

Internationally, hymenopteran insects are worldwide in distribution and often constitute a major part of a region’s insect fauna. Honeybees are exploited for their honey throughout the world; even the aggressive A. m. scutellata is used for honey production in Africa. Honeybees in southern Asia attach huge nests to limbs of forest trees. The giant bee Apis dorsata of Southeast Asia has a reputation for savagery, and deaths from multiple stings have occurred. Yellowjackets and hornets are common in Europe and the Middle East, where their medical importance is similar to that in the United States. The genera Vespula, Vespa, and Dolichovespula are found all over Europe.⁸² The genus Polistes, present throughout central Europe, is not found in the United Kingdom and represents a larger clinical problem in areas surrounding the Mediterranean Sea. Amino acid sequencing of the venom allergens of the different species of Polistes in Europe shows them to be very similar, but the similarities to American strains are less pronounced.¹¹⁸

Two species, Vespula orientalis and Vespula vulgaris, have recently been introduced into Australia, where they have become significant problems.⁶³ Paper wasps of the genus Polistes are plentiful in tropical America and Australia (Figure 50-13). Another Australian paper wasp, Ropalidia revolutionalis, constructs nests that resemble belts of bullets and hangs them from shrubs and fences. Fire wasps (Polybia) are found from Mexico to northern South America. The common species are black with yellow markings. They construct globular, cylindric, or cone-shaped paper nests up to 70 cm (28 inches) long that are hung usually from trees and sometimes under bridges. They may defend these nests with great vigor.

FIGURE 50-13 Wasp colony

(Courtesy Wikimedia Commons.)

Ants

Ants are social insects, worldwide in distribution over a wide range of habitats. Many ants sting, and others have repugnant secretions. The ant species of greatest medical significance in the United States is the imported fire ant Solenopsis invicta (see Figure 50-1, E).¹⁸³ It was apparently introduced from South America into Mobile, Alabama, in 1939 and has subsequently spread throughout the southern states from southeastern Virginia to central Texas and Oklahoma, largely eliminating another introduced fire ant (Solenopsis richteri) and two native species. Mound nests are usually found in open grass settings, often in urban areas (Figure 50-14). Other states that harbor fire ants include Arizona, California, New Mexico, Oregon, and Washington, as well as Puerto Rico. As many as 600 mounds per acre have been reported. Worker colonies may reach a maximum size of 500,000 ants in 2 years and rapidly give rise to satellite colonies.³⁴¹ S. invicta are extremely irritable insects. They are usually easy to identify, as they do not fly away but instead grasp their victims with their mandibles and inflict multiple painful stings.¹⁹³

FIGURE 50-14 Fire ant mound.

Species other than imported fire ants can cause severe reactions.¹⁹² Harvester ants (Pogonomyrmex species) of the southwestern United States and Mexico are of medical importance. Entrances to the underground nests are usually surrounded by clear zones and sometimes by rings of soil. Some species react aggressively to disturbance of the nest. The stings are painful and may be accompanied by systemic symptoms; anaphylaxis has been reported.

There are numerous stinging species of ants in the tropics. Although native to South America, fire ants do not seem to be a major medical problem there, perhaps because of native competitors, predators, and parasites. Two fire ant species are important in areas outside the United States. Solenopsis geminata has been introduced into Okinawa and Guam and is widespread in Central America, Mexico, and some Caribbean islands. Solenopsis xyloni is common in Mexico and also occurs in California and Texas. Anaphylaxis caused by imported fire ants has also been described in Australia.³³⁸ Severe human urticaria produced by the ant Odontomachus bauri has been reported in Venezuela.³⁰⁷ Amino acid sequences of all fire ant venoms are very similar.¹⁶⁸ Therefore, all fire ant stings can be managed medically in the same manner.

The samsum ant, Pachycondyla sennaarensis, is an ecologic counterpart of the fire ant that is widely distributed in the African tropics and the Arabian Peninsula. It nests in the ground but does not make a conspicuous mound. In the United Arab Emirates, it is plentiful in urban areas and may cause multiple stings.^6,⁹⁶ Australian bull ants (Myrmecia species), such as the “jumper jack,” are large insects (about 20 mm [0.8 inches] or the size of a medium cockroach) with prominent jaws (Figure 50-15, A and B).²⁹⁸ They are ground dwelling and common in suburban areas in southeastern Australia. Many neotropical stinging ants live in trees. The giant black ants (16 to 22 mm [0.7 to 0.9 inches]) of the genus Paraponera are found from Nicaragua to the Amazon basin. Although they nest in the ground, workers forage in trees from almost ground level to high in the forest canopy. They are most active at night. The green tree ant of northeastern Australia makes a leaf nest in trees. It has no true sting but ejects formic acid into wounds made by its jaws.

FIGURE 50-15 A, Red bull ant. B, Australian jumper jack ant.

(Courtesy Wikimedia Commons.)

Hymenoptera Stinging Patterns

Multiple stings often result from disturbance of a nest, as the first insects encountered release alarm pheromones that incite aggressive behavior in other members of the colony. With large species such as the white-faced hornet, 40 to 50 stings may create a life-threatening injury.³⁶⁹ The lethal dose of honeybee venom has been estimated at 500 to 1500 stings.³³⁰ However, most of the 40 to 50 deaths per year in North America from Hymenoptera stings are the result of anaphylaxis occurring in victims with prior stings who developed specific immunoglobulin E (IgE) antibodies.¹³² In the United States and other Western nations, the incidence of serious insect stings is higher in adults than in children, and higher in males than in females. Most persons are stung while engaged in outdoor work or recreation. Beekeeping is a high-risk occupation; however, many beekeepers develop considerable immunity as a result of frequent stings.²⁵⁰ Other relatively high-risk occupations include farmers, house painters, carpenters, highway workers, bulldozer operators, and emergency personnel during flooding disaster relief.⁹⁴ Wasps and bees are sometimes swept into the interior of a moving automobile, exposing the occupants to risk of both a sting and a highway accident. Many foods, particularly meats, ripe fruit, or fruit syrups, attract yellowjackets, which often swarm around picnic areas and recycling bins. Syrups, flowers, sweat, and some perfumes attract bees. In such aggregations, the insects are not particularly aggressive but may become trapped in clothing or hair. A recent source documented that Africanized bees were more aggressive after exposure to 20% ethanol than to standard sucrose solutions placed in front of their hives.² In temperate zones, the incidence of hymenopteran stings is highest in late summer and early fall, when insect populations are highest.

Fire ants may invade houses during periods of heavy rain and in hot, dry weather as they seek food and water.⁹¹ There have been increasing incidents of fire ant attacks on patients in health care facilities, such as nursing homes, where frail elderly patients are incapable of fleeing for protection.^88,^141,^302,³⁴⁹ In one report, one patient experienced a severe anaphylactic reaction and four patients died within 1 week. The presence of fire ants around immobilized, often cognitively impaired patients seems to be a primary risk for massive fire ant attacks.⁹⁰ Fatal anaphylaxis to indoor native fire ant stings has been described in infants.²⁴³

Venom and Venom Apparatus

Venom is present in many hymenopteran species and is used for both defense and subjugation of prey. The venom apparatus is located at the posterior end of the abdomen and consists of venom glands, a reservoir, and structures for piercing the integument and injecting venom. Venoms of most medically important Hymenoptera are mixtures of protein or polypeptide toxins, enzymes, and pharmacologically active, low-molecular-weight compounds such as histamine, serotonin, acetylcholine, and dopamine. Melittin, a strongly basic peptide, is the principal component of honeybee venom, making up 50% of the dry venom weight. It damages cell membranes through detergent-like action, with liberation of potassium and biogenic amines.⁷⁰ Peptides with similar activity occur in bumblebee venom. Histamine release by bee venom appears to be largely mediated by mast cell degranulating (MCD) peptide. A third peptide, apamin, is a neurotoxin that acts principally on the spinal cord. Adolapin, a recently described bee venom peptide, has antiinflammatory activity, which may explain the effectiveness of bee venom in treating some forms of arthritis. The chief enzymes of bee venom are phospholipase A and hyaluronidase. The former is believed to be one of the major venom allergens and, with melittin, to account for much of the acute lethality. Histamine makes up about 3% of the dry weight of bee venom. The intravenous (IV) median lethal dose (LD₅₀) of honeybee venom for mice is 6 mg/kg. An average sting injects about 0.50 mL of venom containing approximately 0.05 mg of solids.

Intense pain after stings by hornets and other social wasps is largely caused by serotonin and acetylcholine, which constitute 1% to 5% of dry venom weight. Wasp kinins (peptides) contribute to pain production and have strong, brief hypotensive effects. Mastoparans are similar in action to MCD peptide but are weaker. Phospholipase A, phospholipase B, and hyaluronidase are present in relatively large amounts. Unidentified proteins, some of which appear to be major allergens, are also present. A lethal protein in Vespa basalis venom releases serotonin from tissue cells and has hemolytic and phospholipase A activity.¹⁶⁶ The IV LD₅₀ of different hornet venoms for mice ranges from 1.6 to 4.1 mg/kg.

Less is known of venoms of solitary wasps. The venom of Sceliphron caementarium, a mud dauber (Figure 50-16), is comparatively low in protein and contains no acetylcholine, histamine, serotonin, or kinins but does contain several unidentified low-molecular-weight compounds. Its proteins are immunologically different from those of honeybee, yellowjacket, and paper wasp venoms. Philanthotoxin (molecular weight 435) from venom of the beewolf (Philanthus triangulum) acts at the insect’s myoneural junction and has potential value as an insecticide.

FIGURE 50-16 Solitary mud dauber wasp.

Ant venoms show great variation. In the life of the fire ant (S. invicta), venom plays several important roles, including prey capture, defense, and antimicrobial action. The synthesis of fire ant venom is limited to early life, and the injected venom dose appears to be carefully modulated. Older ant workers (foragers) deliver less venom per sting than do middle-age workers (reserves), and the volume from nest defenders is 50% higher than from their counterparts, particularly in the spring.¹⁵⁴ Venoms of more primitive ants (subfamilies Ponerinae, Myrmicinae, and Dorylinae) resemble venoms of social wasps, containing kinin-like peptides, enzymes, and unidentified proteins. In more highly evolved ants (subfamilies Dolichoderinae and Formicinae), a variety of low-molecular-weight compounds (terpenes, ketones, and organic acids) make up the bulk of the secretion, which may be sprayed rather than injected. Venoms of fire ants (Solenopsis species) are composed largely of piperidine alkaloids, which cause histamine release and necrosis in human skin. Proteins make up only 0.1% of the dry weight of fire ant venoms, but they are highly allergenic.^131,¹³² Hyaluronidase and phospholipase activities have been demonstrated.

Clinical Aspects

Hymenoptera stings are most often inflicted on the head and neck, followed by the foot, leg, hand, and arm. Stings in the mouth, pharynx, and esophagus may occur when bees or yellowjackets in soft drink, iced tea, or beer containers are accidentally ingested.^257,³²⁶ A single wasp, bee, or ant sting in an unsensitized individual usually causes instant pain, followed by a wheal and flare reaction, with variable edema. Fire ants typically grasp the skin with their mouthparts and inflict multiple stings. These produce vesicles that subsequently become sterile pustules (Figure 50-17). Multiple Hymenoptera stings may cause vomiting, diarrhea, generalized edema, dyspnea, hypotension, tachycardia, and collapse. Ocular stings with corneal involvement and bilateral ptosis have been described.^7,^261,^334,³³⁵ Widespread necrosis of skeletal muscle with hyperkalemia, rhabdomyolysis, acute tubular necrosis with renal failure, and hepatorenal syndrome with hemolysis have been reported.^62,^188,²¹⁰ Acute renal failure may result from toxic ischemic mechanisms, with hypovolemia or anaphylactic shock, myoglobinuria, or acute tubular necrosis.³⁹ Hemolytic anemia and acute renal failure requiring dialysis have also been described following massive attacks by 600 to 1500 Africanized bees, as well as following wasp stings in children.^73,^74,³⁵⁹ Acute pancreatitis, disseminated intravascular coagulation, and multiorgan dysfunction are also well documented.^75,^89,^122,^129,³⁶⁹ Myocardial infarction, atrial flutter, and atrial fibrillation in previously healthy individuals may follow multiple hymenopteran stings.^* In one case, a 67-year-old man with acute ST-segment elevation myocardial infarction required fibrinolytic therapy.²¹⁶ Possible pathogenic mechanisms include severe hypotension due to hypovolemic shock, and prolonged coronary spasm with subsequent thrombosis of coronary vessels due to release of vasoactive, inflammatory, and thrombogenic substances contained in Hymenoptera venom.⁵³ Cerebral infarction, descending aortic thrombosis, and coagulation abnormalities are also reported.^67,^217,^300,³⁵²

FIGURE 50-17 Fire ant lesions.

Dermatologically, large local reactions spreading more than 15 cm (6 inches) beyond the sting site and persisting for more than 24 hours are relatively common. Formation of large bullae may also occur.²¹⁰ This represents a cell-mediated (type IV) immunologic reaction, although more than one-half of these patients also have IgE antibody against venom or show a positive skin test. Later stings in these individuals usually result in another large local reaction; systemic reactions are rare.³⁷⁸

Allergy is the most serious aspect of hymenopteran stings. Anaphylaxis and related syndromes from this source are relatively common outdoor wilderness emergencies. An estimated 0.4% of the U.S. population shows some degree of clinical allergy to insect venoms, and 40 to 50 deaths are reported annually.²⁹⁴ This number may be underestimated, because not all anaphylactic episodes are recognized or reported. Fatal anaphylaxis due to fire ant stings has also been reported.²⁸⁸ Asymptomatic sensitization, as shown by positive venom skin test, was observed in 15% of 269 randomly selected subjects with no history of an allergic sting reaction.¹⁴⁶ Sensitization is transient but may persist for years. These individuals are at higher risk of systemic allergic reactions than are those with negative skin tests.¹⁴⁷ Recent studies have reported a high prevalence of hypersensitivity symptoms after intake of wine. Wine contains many contaminants. Some of them come from Hymenoptera insects that fall into the wine when grapes are collected and pressed. Patients with allergic symptoms related to wine consumption may have been sensitized to Hymenoptera venom without previous stings.¹¹

Sudden death from insect sting may not always be recognized. One-half of individuals with fatal sting reactions had no documented history of previous systemic reaction.²⁹ Unexplained deaths at poolsides, golf courses, or any recreational area may be caused by unrecognized Hymenoptera envenomations.⁹⁹ Of 142 sera obtained after sudden, unexpected death, 23% contained elevated levels of IgE to at least one insect venom. In contrast, 6% of sera from 92 blood donors contained comparable IgE levels. In eight fatal cases of Hymenoptera sting anaphylaxis, IgE to the putative venom source was elevated in all, although levels were not higher than those of some healthy individuals in the same population.³²⁶ Allergy-specific IgE antibodies to imported fire ants is nearly twice as common in adults living in endemic areas, making these individuals more susceptible to severe anaphylaxis.⁵⁵ Anti–fire ant IgE and elevated serum tryptase were detected in a case of fatal fire ant sting.²⁵⁰ Elevated levels of venom-specific IgE were detected in two fatal cases of wasp sting.³⁵⁷ However, the level of specific IgE antibodies against venoms is not predictive of the severity of anaphylactic reaction, as documented by recent studies conducted to determine the reliability of postmortem specific IgE antibody testing in venom-induced anaphylactic deaths.¹⁶⁹

Wasp and bee venoms contain 9 to 13 antigens, some of which are potent allergens. Available evidence indicates little cross-sensitization between honeybee and wasp venoms. About 50% cross-sensitization occurs between Polistes and other social wasp venoms, and nearly 100% between yellow jacket and hornet venoms. Positive radioallergosorbent test (RAST) reactions to imported fire ant venom were seen in 51% of patients allergic to bee and wasp venoms but without exposure to fire ants. The allergen appears to be identical to antigen 5 of wasp venoms.¹⁶⁷

Examination of the sera of hypersensitive individuals for IgE and IgG antibodies against purified venom proteins indicates that phospholipase A, hyaluronidase, and acid phosphatase are important in honeybee venom, whereas phospholipase A, antigen 5, and hyaluronidase are important in wasp venoms. Antigen 5, a nontoxic protein of unknown activity, is reported to have sequence similarity to mammalian testis, human brain tumor, and certain plant leaf proteins. This may explain anaphylactic reactions to first insect stings.^190,³⁶⁷ Despite the small amount of protein in fire ant venoms, about 12% of persons treated for fire ant stings show systemic allergic reactions, and at least 32 anaphylactic deaths have been confirmed. Four antigens in S. invicta venom have been reported to be allergenic.⁵²

Allergic sting reactions occur remote from the sting site and include flushing, pruritus, papular urticaria,³⁴² hives, and angioedema. In life-threatening reactions, marked respiratory distress with airway edema, hypotension, loss of consciousness, and cardiac arrhythmias may be seen. At least one-half the severe reactions occur within 10 minutes after a sting, and virtually all occur within 5 hours. Most fatalities occur within 1 hour. The interval between the first known sting and the reaction-producing sting is usually less than 3 years, but may be as long as 48 years. In a group of 3236 Hymenoptera-allergic individuals, 61.5% were male and 32.3% had a history of atopy. The mean age was 30.5 years. No correlation existed between systemic reactions and number of stings in the past or number of stings per incident and severity of a systemic reaction. In a series of 138 adults with a history of insect sting anaphylactic reactions, 99 had no anaphylactic reactions to later stings, 17 had more severe reactions, and 22 had mild to moderate reactions.³⁶¹ In another series of 90 adults with previous anaphylactic reactions, 60 had similar reactions when restung, and 23 had more severe reactions.²⁹³ In children age 10 years and younger, life-threatening reactions occur less often than in adults, and repeated sting episodes usually are not increasingly severe. However, 17% of children with a history of systemic bee or wasp sting reactions developed a systemic reaction after a sting challenge test, as did 5% of children who sustained a sting in the field.¹⁵⁹ Children were once thought to outgrow the allergy to insect stings, but there are no reports accurately documenting this theoretical maturation process.^144,¹⁵¹

Fatalities that occur within the first hour after a sting result from airway obstruction, hypotension, or both. In 69% of fatal cases, obstruction of the respiratory tree by edema or secretions was the principal finding at autopsy; in 12%, vascular pathology was the principal finding; and 7% of the victims had primary central nervous system involvement such as petechial hemorrhages, infarction, and cerebral edema.²⁰ Hemostatic defects, including reduction of all clotting factors and release of a thrombin inhibitor, may be seen with insect sting anaphylaxis. Severe fetal brain damage, presumably associated with hypoxia, has been reported. Delayed (3 to 14 days) atypical reactions after hymenopteran stings include serum sickness and Arthus reaction, which are caused by systemic and local effects of antigen–antibody complexes; nephrotic syndrome; thrombocytopenic purpura; grand mal and focal motor seizures; transient cerebral ischemic attacks; Guillain-Barré syndrome; and progressive demyelinating neurologic disease.³¹⁵ Most appear to be immunologically mediated. In one series, elevated IgE to bee or yellowjacket venom was observed in 6 of 13 such patients.^206,²³⁶

Identification of the individual with potentially dangerous allergy to hymenopteran sting is not always possible. Skin testing with hymenopteran venoms is the most sensitive method; RAST for IgE antibody to venoms is less sensitive, but an important complementary test.^143,¹⁹⁶ Serum tryptase and basophil responsiveness to venom allergens are also sensitive indicators and should be analyzed in patients with a history of severe sting reaction.^30,^312,³¹⁹ A small but significant number of individuals with no history of sting reactions have IgE antibody specific for hymenopteran venoms; prevalence of this antibody is higher in summer.³⁸⁵ These methods do not identify all at risk, and antibody levels do not correlate with severity of sting reactions. In a significant number of individuals, particularly children, clinical sensitivity disappears and IgE levels fall virtually to zero 3 to 18 months after a reaction-producing sting. In about 40% of cases, sensitivity may disappear within 3 years.²⁰⁴ Venom antibody (both IgE and IgG) may be found in healthy individuals (40% of beekeepers, 12% of blood donors) with no history of systemic reaction to insect stings.

No unique features distinguish Hymenoptera envenomations in other parts of the world from those in North America. Venoms of the various groups show little geographic variation. This is also true of groups at risk, with the possible exception of a few honey-gathering Asian tribes. The incidence of Hymenoptera sting allergy may be slightly higher in western Europe than in the United States, and fatal allergic reactions may be slightly more common.⁶⁵ Anaphylactic reactions to bee venom are more prevalent in the rural populations closer to the Mediterranean than in western Europe, where urban populations predominate.²⁴⁰

Paraponera ant stings are intensely painful for several hours and may be accompanied by fever and lymphadenitis. Systemic anaphylactic reactions to stings of Australian bull or jumper jack ants, as well as samsum ants, are increasing, with reports of fatalities.^46,²²⁸ Acute renal failure has also been described.¹ Patients with a history of systemic reactions to samsum ant stings have IgE and positive skin test reactions to fire ant venom.⁹⁶

Treatment and Prevention

Treatment of anaphylaxis is conventional. Aqueous epinephrine 1 : 1000 should be administered subcutaneously in the prehospital setting at the first indication of serious hypersensitivity. The dose for adults is 0.3 to 0.5 mL, and for children under age 12 years it is 0.01 mL/kg, not to exceed 0.3 mL. Compared with methylprednisolone alone, early combination of epinephrine helps to further inhibit the diffusion of allergy and inflammation cytokines, and therefore reduce the severity of injury.³⁸⁰ When symptoms are predominantly respiratory, epinephrine by inhalation (10 to 20 puffs for an adult; 2 to 4 puffs per 10 kg [22 lb] of body weight for a child) may provide more rapid relief.²⁴⁶ In the presence of profound hypotension, the patient may be in shock and not adequately perfusing the skin. In this scenario, 2 to 5 mL of a 1 : 10,000 epinephrine solution may be given by slow IV push, or an infusion may be initiated by mixing 1 mg in 250 mL and infusing at a rate of 0.25 to 1 mL/min. If an IV line is delayed or cannot be established, epinephrine may be given intramuscularly, intralingually, or via an endotracheal tube.¹⁴ Two cases of Hymenoptera-induced anaphylactic shock with profound hypotension were successfully resuscitated using 40 IU of IV vasopressin followed by a rapid fluid bolus.¹⁸⁹ Selective inhaled (nebulized) β₂-adrenergic agents, such as albuterol, can also be effective in relieving bronchospasm at doses of 2.5 mg/3 mL of a 0.08% solution. Aminophylline, 5 mg/kg as a loading dose followed by 0.9 mg/kg/hour as an infusion, may relieve bronchospasm not relieved by epinephrine or albuterol.

In the presence of hypotension, IV crystalloid solutions should be infused; pressor agents such as dopamine or norepinephrine may be required. Oxygen, intubation, and mechanical ventilation may be needed to correct airway obstruction. Antihistamines can alleviate symptoms of anaphylaxis but should be used only in addition to epinephrine, not as a substitute.¹⁴ Corticosteroids are also indicated in acute anaphylactic reactions, although the time of onset with corticosteroids is delayed. Propranolol is contraindicated because of the β-adrenergic blockade effect on the bronchioles. Persons taking β-adrenergic blockers may respond poorly to epinephrine. In these cases, administration of glucagon to counteract the beta blockade effect may prove beneficial.³⁰³ Persons with insect sting anaphylaxis require close observation, preferably in the hospital, over a period of 24 hours.²⁴⁶

For mild hymenopteran stings, ice packs often provide relief. Honeybees frequently and yellowjackets occasionally leave a stinger in the wound. Although recommendations were that stingers should be scraped or brushed off with a sharp edge and not removed with forceps, which might squeeze the attached venom sac and worsen the injury, this has been refuted.^304,³⁶⁴ Advice to victims on the immediate treatment of bee stings now emphasizes rapid removal of the stinger by any method.³⁶⁴ Wheal size and degree of envenomation increased as the time from stinging to stinger removal increased, even for a few seconds. The response was the same whether stings were scraped or pinched off after 2 seconds. Home remedies, such as baking soda paste or meat tenderizer applied locally to stings, are of dubious value, although the latter is often regarded as effective. Topical anesthetics in commercial “sting sticks” are also of little value. Topical aspirin paste is not effective in reducing the duration of swelling or pain in bee and wasp stings and may actually increase the duration of redness.¹⁸ Local application of antihistamine lotions or creams, such as tripelennamine, may be helpful. An oral antihistamine, such as diphenhydramine, 25 to 50 mg for adults and 1 mg/kg for children, every 6 hours is often effective.

All fire ant stings can be managed medically in the same manner. No therapy is effective against local effects of fire ant stings, although oral antihistamines and corticosteroids may provide some relief in severe cases. Because infection is common, topical antimicrobials (e.g., mupirocin) and prophylactic oral antibiotics are recommended. Breaking fire ant blisters should be avoided.^69,⁸⁹

Corticosteroids, such as methylprednisolone, 24 mg/day initial dose tapered off over 4 to 5 days, often help resolve extensive local reactions to bee and wasp stings. This may be combined with cold packs and oral antihistamines. Chronic facial edema caused by multiple bee stings has been effectively treated with plastic surgery and liposuction.⁴

Envenomation from multiple hymenopteran stings may require more aggressive therapy. IV calcium gluconate (5 to 10 mL of 10% solution) with a parenteral antihistamine and corticosteroid may be helpful in relieving pain, swelling, nausea, and vomiting. Development of a hyperimmune bee venom antiserum is under investigation.³²³ Hypovolemic shock is managed conventionally. Plasmapheresis was used successfully to treat a person who sustained about 2000 honeybee stings.⁹⁵ Patients should be observed for 12 to 24 hours for coagulopathy and evidence of renal and neurologic damage. Urine output is monitored and urine tested for hemoglobin and myoglobin. Serum potassium, creatine kinase, and lactate dehydrogenase levels should be monitored. Oliguria with myoglobinuria, azotemia, and hyperkalemia are indications for hemodialysis.

Immunotherapy

It is suggested that at least one-half of sting fatalities in patients with a previous history of severe systemic reactions could have been avoided through the timely administration of specific immunotherapy.²⁸ Venom immunotherapy is 75% to 98% effective in preventing sting anaphylaxis.¹⁴³ Immunotherapy should be offered to patients with a history of anaphylaxis after a sting, mastocytosis, and specific IgE antibodies to the agent confirmed by positive skin testing or in vitro assays.^132,²⁰⁹ In addition, venom immunotherapy significantly reduces the size and duration of large local reactions.^145,³²⁹ Desensitization with purified venoms produces an excellent blocking antibody response and prevents anaphylaxis in more than 95% of patients. A protective anti-idiotypic antibody to honeybee venom has been identified.¹⁸⁶ Venoms for desensitization generally available in the United States are honeybee, yellowjacket, wasp (Polistes), and mixed vespid. More than one venom can be given concurrently, but this requires multiple injections. Commercial preparations consisting of a mixture of yellowjacket, white-faced hornet, and yellow hornet venoms are available.¹³² A whole-body extract of fire ant containing at least three venom antigens has also been developed.³⁶⁸

Children under 16 years with only cutaneous or mild systemic allergic reactions and persons with a history of only large local reactions do not need immunotherapy.²⁵⁴ Evaluation of anaphylaxis risk is recommended in children using wasp venom extract challenges.³²¹ As mentioned previously, children were once thought to “outgrow” their allergies to insect stings, but this has never been proved. In fact, a clinically important number of children retain their allergic reactions to Hymenoptera venom. Immunotherapy in children leads to a significantly lower risk of systemic reaction to stings, even 10 to 20 years after treatment is completed. This prolonged benefit is greater than that observed when the immunotherapy is given to adults.^144,¹⁵¹ Persons receiving β₂-adrenergic blockers should be shifted to other appropriate medications if possible.

Regimens for desensitization attempt to achieve tolerance to venom doses of about 100 mcg. It requires about 95 days to achieve a maintenance level of immunity. Rapid or “rush” programs requiring 3 to 7 days for initial immunization appear to be effective in high-risk patients.^24,^104,^180,^344,³⁷¹ A recent study suggests that an ultra-rush sublingual immunotherapy may be as efficacious and better tolerated than traditional subcutaneous immunotherapy.²⁷⁴ Some programs make use of both active and passive immunotherapies.²⁴⁵ In a series of 1410 patients, 12% had systemic reactions during treatment, but no fatalities were reported.^213,²¹⁴ A report of 26 women with 43 pregnancies does not suggest significantly increased risk from venom immunotherapy during pregnancy.³²⁵ Maintenance doses are required at intervals after basic immunization. Neither skin testing nor determination of IgG and IgE antibody levels against venom will reliably indicate success of immunization, although the majority of persons will be protected by a specific IgG antibody level of 400 RAST units/mL of serum. Actual sting challenge is the most reliable test for determining immunotherapy candidates and desensitization,³⁶² but this is not widely used in the United States. It must be done in the hospital with careful monitoring and consideration of economic, ethical, and safety factors.³¹¹ If the skin test is negative after 3 years of immunotherapy, patients may be placed on immunologic surveillance. Few patients require more than 5 years of immunotherapy.²⁹⁴ According to some authorities, if a sting challenge or field sting is tolerated during the period of immunotherapy, treatment can be terminated after 3 to 5 years.²⁸⁹ For unknown reasons, desensitization to wasp venoms is achieved more quickly than to honeybee venom.³⁶ Although the low mortality and morbidity associated with patients who suffer subsequent stings following immunotherapy has led some to conclude that many patients are being treated unnecessarily, this conclusion is refuted by the fact that venom immunotherapy improves the quality of life and health of the vast majority of patients receiving this intervention.^268,²⁶⁹ Patients should be warned that the efficacy of venom immunotherapy might be less than optimal and they should continue to carry adrenaline auto injectors.²⁵⁶

Like bee venom immunotherapy, purified Myrmecia ant venom immunotherapy has been established and shown to be highly effective for Australian bull or jumper ant and imported fire ant anaphylaxis.^40,^43,^44,^160,²²⁸

Antivenom Therapy and Future Interventions

A group in the United Kingdom has developed ovine Fab-based antivenom as a potential treatment for mass bee stings. Sera from sheep immunized against the venom of A. m. scutellata contained high levels of specific antibodies, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and chromatography. Although effective experimentally in a mouse model, no human administration of the antivenom has been documented.¹⁷⁹

Another approach based on genetic engineering is the use of non-IgE binding peptide fragments of the insect allergen with preserved T-cell epitopes for advanced immunotherapy. Such preparations of bee venom phospholipase A2 have been used successfully in pilot studies. Additionally, DNA vaccination with phospholipase A2 sequence plasmids has been proved effective in a mouse model.²⁴⁴

Patients who experience severe anaphylaxis to venom immunotherapy can now be treated with the anti-immunoglobulin (Ig) E monoclonal antibody, omalizumab.¹³⁵

Preparedness and Preventive Measures

Persons with a history of allergic reactions to insect stings (including large local reactions) should carry an emergency kit containing epinephrine autoinjectors and should wear medical identification tags.¹³² Kits should be available in work and recreation areas where the risk of insect sting is high. Two kits widely available in the United States are EpiPen and Ana-Kit. EpiPen and EpiPen Jr. are autoinjectors that deliver 0.3 mg or 0.15 mg of epinephrine, respectively (Figure 50-18, online). They are quick and easy to use; however, patients should be cautioned against injecting the material into fingers or buttocks or directly over veins. Ana-Kit contains two doses of 0.3 mg of epinephrine in a single conventional syringe, plus chewable antihistamine tablets and a tourniquet. It is more versatile but requires more instructions for the user. Twinject is another product that may be used to inject two doses of epinephrine.

FIGURE 50-18 EpiPen preloaded delivery system for injection of aqueous epinephrine.

(Courtesy Dey, LP.)

Frequent cleaning of garbage cans and disposal of decaying fruit makes premises less attractive to bees and wasps. Hymenopterans are highly susceptible to many insecticides, and their control around dwellings and other inhabited buildings is rarely difficult. Spraying the nests after dark is safer because these insects are less active at night. Many hymenopterans are economically valuable as pollinators of plants or predators on other insects, so their control on a wide scale is rarely desirable. The fire ant in the southern United States has been the target of massive but marginally effective control campaigns that adversely affected local ecosystems. A new approach uses grain baits containing synthetic insect growth hormones that are carried into the nests, where they disrupt ant caste differentiation and inhibit egg production. Arrays of thousands of hormone-baited traps placed in select areas of Mexico, however, failed to stop the northward spread of Africanized bees. For controlling populations of Africanized bees, care should be taken that items such as boxes and empty oil drum containers are not left outdoors. Ceilings and walls should be sealed off as potential nesting sites for colonies and swarms.⁸⁰

Lepidoptera

Venomous Species and Venoms

Next to flies, lepidopterans are the most abundant arthropods, with more than 165,000 species worldwide, with most species posing no human threats. However, caterpillar species from approximately 12 families of moths or butterflies can inflict serious human injury.⁹³ Insects of the order Lepidoptera may cause human envenomation that is generally less serious than that with hymenopterans. Injury usually follows contact with caterpillars and is less frequent with the cocoon or adult stage. The larval lepidopteran (caterpillar) is usually free living, is moderately active, and feeds on plants, although a few are parasites of insect nests or eat food of animal origin. The pupal stage may be free or encased in a silk cocoon. Wintering over in cold climates is usually in the pupal stage. Adults (butterflies and moths) have wings with microscopic chitinous scales. They feed primarily on nectar and other plant juices, but some eat semiliquid mammalian feces and urine. The adult provides no care or protection of immature stages. No social organization exists, although larvae and adults of some species assemble in large aggregations.

Many venomous caterpillars are broad, flat, and sluggish. Some have the dorsal surface densely covered with long hairs. Others are spiny and may have bright, conspicuous colors and markings. Some are highly camouflaged.

Venoms in Lepidoptera are purely defensive. The venom apparatus consists of spines that are simple or branched and frequently barbed. They may be scattered widely over the surface of the insect or arranged in clumps and often are intermixed with nonveniferous hairs or spines. In the most venomous caterpillars, the spines are hollow and brittle with venom glands at the bases. Muscles surrounding the glands may help in expelling venom. In other Lepidoptera, the spines are solid and function primarily as mechanical irritants or contain surface toxicants. Little is known of the chemistry of caterpillar venoms. Some are heat labile and contain proteins. Histamine and serotonin have been found in caterpillar venoms but are not common. Hairs of the brown-tailed moth (Euproctis chrysorrhea) contain enzymes with esterase and phospholipase activity.

Probably the most important venomous caterpillar in the United States is the puss caterpillar.^139,³²⁸ It is also known as the asp caterpillar¹⁰⁶ or woolly slug (Megalopyge opercularis) (Figure 50-19). This caterpillar is distributed throughout most of Texas, Louisiana, Florida, and north to Maryland and Missouri. The hairy, flat, and ovoid caterpillar reaches a length of 30 to 35 mm (1.2 to 1.4 inches) and feeds on shade trees, including elm, oak, and sycamore. Some years it may be plentiful enough to be a nuisance. In southeast Texas in 1958, 2130 persons were treated for stings, and eight were hospitalized. A related species, the flannel moth caterpillar (Megalopyge crispata) (Figure 50-20), occurs in the eastern states north to New England. Its sting is less severe than that of M. opercularis. The large, spiny caterpillar of the io moth (Automeris io)¹¹⁷ is pale green with red and white lateral stripes (Figure 50-21). It is widely distributed in the eastern United States, but rarely plentiful. The saddleback caterpillar¹¹¹ (Sibine stimulea) (Figure 50-22) and oak slug (Euclea delphinii) are flat and almost rectangular; both can deliver a painful injury. The gypsy moth (Lymantria dispar) (Figure 50-23) feeds on a variety of plants and has caused thousands of cases of dermatitis in the northeastern United States. These caterpillars have also been imported to Europe across the Atlantic Ocean on exported house or garden plants.⁶⁸ Other common nettling caterpillars are E. chrysorrhea, which also occurs in Europe, and the tussock or toothbrush caterpillar (Hemerocampa leucostigma), with its conspicuous red head and four tufts of bristles. Another tussock caterpillar, Oryia pseudotsuga, causes numerous cases of dermatitis and conjunctivitis among lumberworkers and foresters in the northwestern states. The hickory tussock caterpillar (Lophocampa caryae) can cause skin irritation and urticaria with dermal contact, or drooling if ingested (Figure 50-24).^200,²⁸⁵ The eastern tent caterpillar, Malacosoma americanum (Figure 50-25), is native to North America. Populations fluctuate from year to year, with outbreaks occurring every several years. Defoliation of trees, building of unsightly silken nests in trees, and wandering caterpillars crawling over plants, walkways, and roads cause this insect to be considered a pest in the late spring and early summer. Eastern tent caterpillar nests are commonly found on wild cherry, apple, and crabapple trees, but may be discovered on other various fruit trees.

FIGURE 50-19 Puss caterpillar, Megalopyge opercularis.

FIGURE 50-20 Flannel moth caterpillar, Megalopyge crispata.

FIGURE 50-21 Caterpillar of the io moth, Automeris io. Widespread in the eastern United States, this species can inflict a painful sting.

FIGURE 50-22 Saddleback caterpillar, Sibine stimulea.

FIGURE 50-23 Gypsy moth, Lymantria dispar.

(From Wikimedia Commons.)

FIGURE 50-24 Hickory tussock moth caterpillar, Lophocampa caryae.

(Courtesy EDUPIC Graphical Resource.)

FIGURE 50-25 Eastern tent caterpillar, Malacosoma americanum.

(Courtesy Richard Seaman. http://www.richard-seaman.com.)

Stinging Patterns

Lepidoptera are uncommonly recognized causes of localized stings, eczematous or popular dermatitis, and urticaria.¹⁷² Caterpillar envenomation usually occurs when living insects are touched as they cling to vegetation or drop onto bare skin. Persons cutting branches, picking fruit, or climbing trees are likely to be stung. However, the largest outbreaks have been associated with spines detached from live or dead caterpillars and cocoons. These may be airborne or deposited on bedding or laundry hung outdoors. In temperate regions, caterpillar stings are most common from August to early November. Heavy caterpillar infestations seem to occur during exceptionally favorable weather and with decreases in populations of parasites and predators that serve as natural controls.

Clinical Aspects

Two general syndromes are associated with lepidopteran envenomations. In the cases of caterpillars with hollow spines and basal venom glands (e.g., Automeris, Megalopyge, and Dirphia), direct contact with the live insect causes instant nettling pain, followed by redness and swelling (Figure 50-26). Puss caterpillar stings show a characteristic gridiron pattern of hemorrhagic pinpoint papules. In typical cases, no systemic manifestations occur, and symptoms usually subside within 24 hours. However, pain may be intense with central radiation, accompanied by urticaria, nausea, headache, fever, vomiting, muscle spasms, paresthesias, and lymphadenopathy. Hypotension, shock, dyspnea, abdominal tenderness, and convulsions have been reported with more severe cases of puss caterpillar stings.^117,^137,^139,^170,³²⁸

FIGURE 50-26 Nettle rash from unidentified caterpillar.

The second syndrome is associated with caterpillars with a less highly developed venom apparatus (e.g., Lymantria, Euproctis, Thaumetopoea). Contact with the living insect is not necessary; detached spines are often involved. Little or no immediate discomfort is experienced. An itching, erythematous, papular, or urticarial rash develops within a few hours to 2 days and persists for up to a week (Figure 50-27). Rarely, the lesions may be bullous. Conjunctivitis, upper respiratory tract irritation, and rare asthma-like symptoms may be seen with or without dermatitis. Ophthalmia serious enough to require enucleation may be caused by detached spines lodged in the eye. Acute anaphylactic reactions have not been reported to follow lepidopteran stings. Patch testing has demonstrated both immediate and delayed hypersensitivity. A pediatric case series reported 10 patients who ingested various caterpillar species. Adverse effects ranged from mild (drooling and refusal to drink) to diffuse urticaria. Five of the patients underwent direct laryngoscopy and endoscopy to assess for pharyngeal and esophageal injuries. None had adverse outcomes.¹⁹⁴

FIGURE 50-27 Lepidopterism. A, Toxic irritative caterpillar dermatitis. B, Silken nest on the trunk of an infested oak tree with living larvae. C, Sixth larval instar of Thaumetopoea processionea L. D, Setae (×200).

(From Spiegel W, Maier H, Maier M: A non-infectious airborne disease, Lancet 363:1438, 2004.)

The pine processionary caterpillar has been reported to cause significant local reaction and airway compromise mimicking an allergic event in children with oral ingestions.¹⁷⁵

Treatment and Prevention

Treatment of lepidopteran envenomations is symptomatic. Prompt application and stripping off of adhesive tape or a commercial facial peel at the site of the sting may remove many spines and serve as a diagnostic procedure, as the spines can then be identified by microscopy (Figure 50-28). Patients with local symptoms usually obtain relief from group I corticosteroid creams, oral antihistamines, and ointments.¹⁷¹ Over-the-counter preparations containing corticosteroids and antihistamines are not significantly better than simpler preparations such as calamine lotion with phenol. Oral antihistamines such as fexofenadine (60 mg, twice a day) or antiinflammatory drugs such as tolmetin sodium (400 mg, three times a day) are often effective in more severe cases. Occasionally, codeine (30 to 50 mg) or oxymorphone (1.5 mg) in combination with an antiemetic may be needed to control pain and vomiting. Intravenous calcium gluconate has been used successfully in severe puss caterpillar envenomation to control muscle spasms.^255,²⁸³

FIGURE 50-28 Microscopic view of Lepidoptera spines.

(From http://www.microscope.mbl.edu.)

Trees on which caterpillars feed may be sprayed with appropriate insecticides to control species such as the puss caterpillar. Screens on windows and doors protect against moths with toxic spines.

Internationally, Lepidoptera show high diversity in the tropics with correspondingly greater medical importance, particularly in Latin America. Caterpillars of the genus Lonomia, native to northern South America, especially Venezuela and the southern region of Brazil, can inflict life-threatening stings ⁵⁶ (Figures 50-29 and 50-30). These caterpillars are 50 to 70 mm (2 to 3 inches) long and have numerous branched dorsal spines. They live in primary tropical forests in groups of up to 50 individuals. Disturbance of their habitat has resulted in an increasing number of envenomations. Stings cause intense pain but not much local reaction. Venom of Lonomia is a protein that activates prothrombin and is stimulated by factor V and calcium ions.¹⁵² Signs of coagulopathy, such as ecchymoses, bleeding gums, hematuria, and melena, may develop in a few hours or be delayed for several days. The venom-induced hemolysis or hemorrhagic syndrome results from prothrombin and factor X and promotes fibrinogenolytic activity and massive fibrinolysis.^173,²²² Fibrinogen, factor V, factor XII, and plasminogen are decreased, fibrin degradation products are increased, and platelets usually are normal. Acute renal failure,^34,⁴⁷ cerebral hemorrhage, and pulmonary hemorrhage may occur. Coagulopathy may last 2 to 5 weeks. In one series of 33 cases, four were fatal.^12,^47,¹⁰³ Treatment with prednisone, plasma, and whole blood is ineffective. An antivenom has been developed, and preliminary reports indicate possible clinical efficacy.^76,⁷⁹

FIGURE 50-29 Caterpillar of Lonomia achelous, which can inflict injuries characterized by potentially fatal coagulopathy.

FIGURE 50-30 Moth of Lonomia achelous, which has no venomous spines.

Neotropical caterpillars of the genera Dirphia, Megalopyge, and Automeris are large, stout, spiny, and sometimes covered with hair. Most are forest species but can adapt to areas of cultivation. Agricultural workers are most often stung and the incidence of stings is higher in the rainy season. Intense, centrally radiating pain with local edema, erythema, and lymphadenopathy is typical. Systemic symptoms include nausea, headache, malaise, chills, and fever. Hypotension, shock, and convulsions have been reported. An Automeris caterpillar bite reported from French Guyana produced syncopal pain and edematous infiltration of the thigh lasting several days.⁷¹ Symptoms usually subside within 24 hours. Treatment is symptomatic. Oral antihistamines are often effective if given within an hour after the sting. Opioid agents are occasionally needed to control pain. A chronic granuloma known as pararama occurs on the hands of Brazilian rubber tappers after contact with Premolis semirufa caterpillars. Permanent extremity disability may result.²⁸⁰

Moths of the genus Hylesia are found from southern Mexico to Argentina. The caterpillars have venomous spines, but the greatest problem is created by the moths, which have a coating of spines on their abdomen. The spines or setae are hollow and pointed, contain a toxin of unknown nature, and are freely shed into the air. The moths are attracted to lights in enormous numbers, and their airborne spines can cause great discomfort. Their activity has created serious problems at airports, shipping docks, and tourist resorts. Within a few minutes to a few hours after contact with the spines, victims develop a pruritic, erythematous rash that progresses to urticaria and excoriation. Any portion of exposed skin may be involved, but palms and soles are often spared. Irritation of eyes and mucous membranes is unusual. Symptoms subside in about a week if there is no further exposure. Topical and systemic treatments have had little benefit.⁹⁷

In Korea, outbreaks of dermatitis, presumably caused by setae of the yellow moth Euproctis flava, are well known. In the summer of 1980, hundreds of U.S. soldiers were affected.²³ The caterpillars feed on hardwood trees, and great numbers of moths appear in summer and are attracted to lights. Dermatitis usually involves direct contact with moths or their cocoons or with clothing contaminated with setae. The lesions are similar to those described for Hylesia and are equally refractory to treatment. Other outbreaks of dermatitis ascribed to Euproctis moths and caterpillars have been reported in Japan and China. One outbreak in Shanghai in 1972 affected about 500,000 individuals. Outside Shanghai, where chemical insecticides would have been harmful to silkworm culture, Euproctis caterpillars (Figure 50-31) have been controlled by spraying with an insect virus. Cases of Euproctis dermatitis and ophthalmia have also been reported in Australia and Great Britain. Sensitization with elevated IgE levels may occur.^280,³³⁹

FIGURE 50-31 Euproctis caterpillar.

(Courtesy Walwyn.)

In the Mediterranean region and the Middle East, the pine processionary caterpillars Thaumetopoea pityocampa and Thaumetopoea wilkinsoni are plentiful and make silk nests in trees. The setae from these caterpillars can cause a maculopapular rash accompanied by urticaria, bronchitis, and conjunctivitis. A non–IgE-mediated release by Thaumetopoea results in a type I hypersensitivity foreign-body reaction, resulting in dyspnea and bronchospasm.³⁴⁰ Outbreaks typically occur when groups of tourists or military personnel camp in pine groves. The rash usually results from contact with detached setae rather than with caterpillars. The adult moth stage apparently does not have irritating spines. Systemic reactions manifesting as abdominal pain and hypertension have been reported.¹⁹⁸

Moths of the genus Calyptera, native to Southeast Asia, have a serrate proboscis and feed on mammalian blood, including that of humans. Tropical species of several moth genera feed on human ocular secretions. Their medical importance is unknown. In Australia, five families of caterpillars that inflict lesions resulting in local pain and urticaria have been described (Arctiidae, Limacodidae, Anthelidea, Lymantriidae, and Spingidae). All dermal reactions were responsive to ice packs and antihistamines. Ingestions resulted in no adverse side effects.¹⁶ Contact dermatitis or erucism has been described in New Zealand from exposure to gum leaf skeletoniser (Uraba lugens) caterpillars in the Auckland region.⁸⁷

Centipedes and Millipedes

Centipedes are elongate, flattened arthropods with one pair of legs for each of the typical body segments, which may number from 15 to more than 100. The first segment bears a pair of curved hollow fangs with venom glands at the bases. The last segment bears a pair of filamentous to forceps-like caudal appendages not associated with the venom apparatus.³⁴ The largest species reach lengths of about 30 cm (12 inches). Most centipedes live in crevices or beneath objects on the ground. Some are burrowers and others are climbers. Many are nocturnal. Scutigera coleoptrata, with a body length of 25 mm (1 inch) and long thin legs, is a common house arthropod in much of the United States. Lithobius is a cosmopolitan ground-dwelling genus. A species common in eastern U.S. gardens is orange and 30 to 50 mm (1.2 to 2 inches) long. Envenomations by imported varieties of the Vietnamese centipede have been reported in Long Island, New York.²²⁷ Centipedes prey chiefly on invertebrates, but larger species occasionally eat small vertebrates. Female centipedes of some species curl around their egg clusters and newly hatched young, and may actively defend them.

Centipedes use venom primarily to kill prey and only secondarily for defense. Venom may also have a digestive function. Enzymes, including acid and alkaline phosphatase and amino acid naphthylamidase, lipoproteins, histamine, and serotonin, are variably present.²⁴¹ Venom of Scolopendra subspinipes produces hypotension followed by hypertension. The major lethal toxin is an acidic protein with a molecular weight of 60,000 daltons. It produces vasoconstriction, increased capillary permeability, and cardiotoxicity.^148,¹⁴⁹

Like spiders, any centipede whose fangs can penetrate human skin can cause local envenomation. Centipede bites are typically pointed in shape, a feature that can help differentiate the bite of a large centipede from that of a snake.^109,²¹¹ Contrary to popular folklore, centipedes do not inject venom with their feet or caudal appendages. The jaws inject a neurotoxic venom through venom ducts. Centipede bites have been reported from numerous tropical and subtropical regions but never as a serious medical problem. Most bites have been ascribed to species of Scolopendra, which has a wide distribution with several species in the southern United States (Figures 50-32 and 50-33). Fatalities are almost unknown; however, a death in the United States was recently mentioned, but the locality and other details were not given.²⁰³

FIGURE 50-32 Centipede, Scolopendra heros.

FIGURE 50-33 Centipede fangs.

Burning pain, local swelling, erythema, lymphangitis, and lymphadenopathy are common manifestations of a centipede bite. Some theorize that there is a close relation between centipede allergy and bee or hymenoptera venom allergy.¹⁵⁸ Swelling and tenderness may persist for as long as 3 weeks or may disappear and recur. Severe and prolonged symptoms have been described in patients with sickle cell disease.³¹⁰ Superficial necrosis may occur at the site of fang punctures. Few bites result in cellulitis, necrotizing fasciitis and serious systemic reactions.³⁵⁸ In one case ascribed to Scolopendra heros in the southwestern United States, a woman had massive edema of the leg, necrosis of the peroneal muscles, loss of motor function in the foot, myoglobinuria, and azotemia.²¹⁵ An Israeli patient bitten on the neck complained of inability to turn her head, probably because of muscle spasm.²⁴¹ Other cases have been characterized by dizziness, nausea, collapse, and pyrexia.²⁴⁷ An infant who ingested a centipede identified as Scutigera morpha developed hypotonia, vomiting, and lethargy, presumably from being bitten in the mouth or pharynx. The child recovered spontaneously after about 48 hours.²¹ Centipede envenomation in a newborn inflicted by Scolopendra gigantean was reported in Venezuela and caused crying, irritability, and localized wound edema.³⁰⁶ Cryptops and Otostigmus genera are responsible for most cases of centipede stings.²³¹ Acute coronary ischemia associated with myocardial infarction with electrocardiographic changes and elevated cardiac troponin has been described after envenomation from an unidentified centipede in Turkey.^270,³⁸¹

Although some centipede bites may be excruciatingly painful, they are not fatal and seldom require more than supportive care. Treatment of centipede envenomation is symptomatic. Ice packs, hot water immersion, and analgesics all can improve pain from centipede envenomation.⁵⁴ Infiltration of the bitten area with lidocaine or another anesthetic promptly relieves pain. Antihistamines and corticosteroids have been suggested for more severe reactions. Tetanus prophylaxis is advisable.^51,²⁴² Hot water immersion has proved beneficial in Australia from bites of centipedes from the genera Scolopendra, Cormocephalus, and Ethmostigmus.¹⁷

Millipedes

Millipedes differ from centipedes in having two pairs of legs per body segment and in lacking apparatus for injecting venom. Several large species of the genus Spirobolus are common in the southern United States (Figure 50-34). Some species are broad and short and roll into a ball when disturbed (Figure 50-35). The millipede species Illacme plenipes found in California comes the closest to having its namesake’s mythical 1000 legs—individuals can bear up to 750 legs.²²³ Millipedes are generally ground dwelling and secretive. Occasionally, they aggregate in enormous numbers. They generally feed on decaying vegetation.

FIGURE 50-34 Spirobolus millipede.

FIGURE 50-35 Giant Madagascar millipede.

Millipedes are exceptionally well endowed with defensive chemical secretions that include hydrogen cyanide, organic acids, phenol, cresols, benzoquinones, and hydroquinones. These effectively deter most predators. Some large species can eject secretions for distances up to 80 cm (32 inches).

Human injury from millipede secretions has been reported from a number of tropical regions.¹⁶² The most common injury is dermatitis that begins with a brown-stained area, which burns and may blister and exfoliate.²²⁴ Millipede burns have been described in unusual sites with pediatric cases mimicking child abuse.⁷⁸ Millipede secretion in the eye causes immediate pain, lacrimation, and blepharospasm. This may be followed by chemosis, periorbital edema, and corneal ulceration. Blindness has been reported.¹⁵⁷ Individuals exposed to large millipede aggregations may complain of nausea and irritation of the nose and eyes. No specific treatment is available. Prompt irrigation with water or saline should be followed by analgesics, antimicrobials, and other measures appropriate for superficial chemical burns. Ophthalmologic evaluation is mandatory for eye injuries. Infestation of the human intestines by the millipede Nopoiulus kochii has been described in Turkey. Antiparasitic drugs (niclosamide and albendazole) may not be effective in eradicating the problem.¹¹⁴

Hemiptera (Sucking Bugs)

Hemiptera is a large order of insects characterized by sucking mouthparts, generally in the form of a beak, and a life cycle with no well-demarcated larval and pupal stages but a gradual transition from the hatchling nymph to adult. Most hemipterans are winged as adults, with the anterior wings generally divided into chitinized and membranous sections. Most feed on plant juices, but several families are predators, and two feed on the blood of humans and other vertebrates. Hematophagous bugs are able to exploit the temperature differences observed over the skin surface to locate blood vessels. These bugs generally bite into the warmest temperature regardless of the target or background temperature.¹¹⁹

The assassin bugs (family Reduviidae) are generally recognized by their long and narrow head, a stout and three-jointed beak, long antennae, and typical hemipteran wings (Figure 50-36). Most are of a dark color; a few are brightly marked or have a checkerboard pattern along the posterior edge of the abdomen. Some species attach fragments of their prey, sand grains, or other debris to their backs. Reduviidae occur on all continents. They have a variety of habitats and are often nocturnal.