3605 Disorders Caused by Venomous Snakebites and Marine Animal Exposures CHAPTER 460

warm, sterile saline. Bleeding is generally controlled with local

pressure. Most wounds should be left open to heal by secondary

intention or treated by delayed primary closure. Early primary

repair is occasionally preferred for cosmetic reasons but increases

the risk of wound infection. Tetanus immunization should be provided as appropriate. Antibiotic treatment should be considered

for serious wounds and for envenomations in immunocompromised hosts. The initial antibiotics should cover Staphylococcus and

Streptococcus species. If the victim is immunocompromised, if a

wound is primarily repaired, or if an infection develops, antibiotic

coverage should be broadened to include Vibrio species for wounds

sustained in salt water or Aeromonas species for wounds sustained

in freshwater.

APPROACH TO THE PATIENT

Marine Envenomations

It is useful to be familiar with the local marine fauna and to recognize patterns of injury.

Coelenterate (marine invertebrate) stings sometimes create diagnostic skin patterns. A diffuse urticarial rash on exposed skin

is often indicative of exposure to fragmented hydroids or larval

anemones. A linear, whiplike print pattern appears where a jellyfish

tentacle has contacted the skin. In the case of the box jellyfish, a

crosshatched appearance, followed by development of dark purple

coloration within a few hours of the sting, heralds skin necrosis.

An encounter with fire coral causes immediate pain, erythema, and

swelling in the pattern of contact, similar to but more severe than

the imprint left by exposure to an intact feather hydroid. Seabather’s eruption, caused by thimble jellyfish and larval anemones, is a

diffuse, intensely pruritic rash consisting of clusters of erythematous macules or papules that follow the pattern of bathing attire

(Fig. 460-8). Toxic sponges create a burning and painful red rash

on exposed skin, which may blister and later desquamate. Virtually

all marine stingers cause cutaneous inflammation; thus, local erythema, swelling, and adenopathy are fairly nonspecific.

A large puncture wound or jagged laceration (particularly on the

lower extremity) that is more painful than one would expect from

the size and configuration of the wound is likely to be a stingray

envenomation. Smaller puncture wounds, sometimes associated

with purple or dark discoloration, represent the activity of a sea

urchin or starfish. Stony corals cause rough abrasions and, in rare

instances, lacerations or puncture wounds.

■ SOURCES OF ANTIVENOMS AND

OTHER ASSISTANCE

In the United States, assistance in locating a specific antivenom can be

obtained from a regional poison control center (800-222-1222). Divers

Alert Network, a nonprofit organization designed to assist in the care

of injured divers, also may help with the treatment of marine injuries.

The network can be reached at www.diversalertnetwork.org or by

telephone 24 h a day at 919-684-9111. The antivenoms for box jellyfish

(C. fleckeri) and stonefish or severe scorpionfish envenomations are

made in Australia by Seqirus (63 Poplar Road, Parkville, Victoria,

Australia 3052; www.seqirus.com.au; 61-3-9389-2000). When administering the box jellyfish antivenom, time is of the essence. For cardiac

or respiratory decompensation, a minimum of 1 ampule and up to

6 ampules consecutively should be given IV, preferably in a 1:10

dilution with normal saline. For stonefish or severe scorpionfish

envenomation, 1 ampule of specific antivenom should be administered

IM for every one or two punctures, to a maximum of 3 ampules.

MARINE POISONINGS

■ HISTAMINE (SCOMBROID) FISH POISONING

Histamine fish poisoning, most often referred to as scombroid or pseudoallergenic fish poisoning, may be the most common type of seafood

poisoning worldwide. It was originally described after consumption

of scombroid (mackerel-like) fish (including albacore, bluefin, and

yellowfin tuna; mackerel; saury; needlefish; wahoo; skipjack; and bonito), but is now more commonly reported with consumption of nonscombroid fish (including dolphinfish, kahawai, sardine, black marlin,

pilchard, anchovy, herring, amberjack, Australian ocean salmon, and

bluefish).

Under conditions of inadequate preservation or refrigeration, the

amino acid l-histidine in the musculature of these fish undergoes

decarboxylation to histamine, histamine phosphate, and histamine

hydrochloride by Morganella morganii, Escherichia coli, Proteus species, and Klebsiella species. Histamine levels of 20–50 mg/100 g are

noted in toxic fish, with levels >400 mg/100 g on occasion. Toxic levels

can be reached with as few as 12 h of inadequate refrigeration. The

pathophysiology of this intoxication remains unclear, as large doses of

oral histamine do not reproduce the condition. It has been proposed

that other biogenic amines such as cadaverine and putrescine may

inhibit the metabolism of histamine. Another potential mechanism

is the induction of mast cell degranulation by an unidentified toxin.

However, affected individuals may have normal levels of mast cell–

derived prostaglandins, which argues against this mechanism.

The toxin or toxins involved are heat stable and are not destroyed

by cooking or freezing. Affected fish may have a sharply metallic or

peppery taste, although more often they are normal in appearance,

color, and flavor. Not all persons who eat a contaminated fish necessarily become ill, perhaps because of uneven distribution of decay within

the fish.

Symptoms develop within 15–90 min of ingestion. Most cases are

mild, with tingling of the lips and mouth, mild abdominal discomfort,

and nausea. The more severe and commonly described presentation

includes intense, sharply demarcated flushing of the face, neck, and

upper trunk, pruritus, urticaria, and angioedema. This syndrome may

progress to bronchospasm, nausea, vomiting, diarrhea, epigastric pain,

abdominal cramps, dysphagia, headache, palpitations, tachycardia,

dizziness, hypotension, and cardiogenic shock. Without treatment,

the symptoms generally resolve within 8–12 h. Because of blockade of

gastrointestinal tract histaminase, the reaction may be more severe in a

person who is concurrently ingesting isoniazid.

TREATMENT

Scombroid Poisoning

Therapy is directed at reversing the histamine effect with systemic

antihistamines. In case literature, H2 receptor antagonists (e.g.,

cimetidine, ranitidine) appear to further decrease the severity

and duration of illness when added to H1 receptor antagonists

FIGURE 460-8 Erythematous, papular rash typical of seabather’s eruption caused by

thimble jellyfish and larval anemones. (Courtesy of Paul Auerbach, with permission.)

3606 PART 14 Poisoning, Drug Overdose, and Envenomation

(e.g., diphenhydramine, hydroxyzine). If bronchospasm is severe,

an inhaled bronchodilator (e.g., albuterol) can be used. In rare

cases, parenteral epinephrine may be needed. The use of activated

charcoal is not recommended. Protracted nausea and vomiting

may be controlled with antiemetics (e.g., ondansetron, prochlorperazine). Hypotension should be treated with IV fluids. It is

important to inform the patient that the symptoms are related to

eating improperly refrigerated fish and are not due to a fish allergy.

■ CIGUATERA

Epidemiology and Pathogenesis Ciguatera poisoning is the

most common nonbacterial food poisoning associated with fish in the

United States and accounts for approximately half of all cases. Florida

and Hawaii account for 90% of reported U.S. cases, although, with

transportation of imported fish worldwide, all clinicians need to be

aware of ciguatera. The poisoning almost exclusively involves carnivorous, bottom-dwelling reef fish native to the Indian Ocean, the South

Pacific, and the Caribbean Sea. More than 500 different fish species

have been implicated in ciguatera poisoning, but the most common are

barracuda, snapper, moray eel, grouper, sea bass, and Spanish mackerel.

Global estimates of incidence vary widely from 20,000–500,000 cases

per year; it is suspected that a large majority of cases go unreported.

Ciguatoxins are produced primarily by the bottom-dwelling, photosynthetic marine dinoflagellate Gambierdiscus toxicus. These lipophilic

toxins bioaccumulate in the marine food chain when large carnivorous

fish consume the grazing fish that feed on these dinoflagellates. Ciguatoxins are heat stable and unaffected by freezing, drying, cooking, or

gastric acid. The toxins do not affect the odor, taste, or appearance of

the fish, making identification and prevention difficult. Ciguatoxins are

potent activators of neuronal sodium channels but may also have other

effects such as antagonism of voltage-gated potassium channels. Toxins

are found in the highest concentrations in the fish’s skin, head, and

viscera; therefore, consumption of these portions should be avoided.

Clinical Manifestations Symptoms can develop within 15–30

min of ingestion but more commonly in 2–6 h. Most victims develop

symptoms within 12 h of ingestion, and virtually all are afflicted within

24 h. Numerous ciguatoxins have been identified, and their relative

abundance in different species of fish and geographic regions likely

explains the wide array of reported symptoms (Table 460-3). Early

symptoms include nausea, vomiting, diarrhea, abdominal cramps,

headache, and diaphoresis. Neurologic manifestations include vertigo,

dysesthesia, paresthesia, visual disturbance, dysgeusia, and reversal of

hot and cold temperature discrimination. Some victims describe a sensation of loose teeth. Bradycardia, hypotension, and orthostasis have

also been reported. Gastrointestinal symptoms generally resolve after

24−48 h but neurologic manifestations may persist for days to weeks.

More severe reactions tend to occur on repeat exposure. Persons who

have ingested parrotfish (scaritoxin) may develop classic ciguatera

poisoning as well as a “second-phase” syndrome (after a delay of 5–10

days) of disequilibrium with ataxia, dysmetria, and resting or kinetic

tremor. This syndrome may persist for 2–6 weeks.

Diagnosis Ciguatera poisoning is a clinical diagnosis. The toxin can

be detected by liquid chromatography and tandem mass spectrometry,

and fish suspected of contamination can be tested using a ciguatoxinspecific enzyme immunoassay, but these techniques are generally not

available in most health care institutions. The differential diagnosis of

ciguatera includes paralytic shellfish poisoning, eosinophilic meningitis, type E botulism, organophosphate insecticide poisoning, tetrodotoxin poisoning, and psychogenic hyperventilation.

TREATMENT

Ciguatera Poisoning

Therapy is supportive and based on symptoms. Volume losses from

vomiting and diarrhea should be treated with crystalloids and electrolyte repletion. Hypotension may rarely be unresponsive to fluids

and require vasopressors. Symptomatic bradyarrhythmias generally

respond well to atropine (0.5 mg IV, up to 2 mg). Problematic

orthostasis can be treated with direct alpha-adrenergic agonists

(e.g., phenylephrine). IV infusion of mannitol may be beneficial in

moderate or severe cases in fluid-replete patients; however, the efficacy of this therapy has not been definitively proven. An initial IV

dose of mannitol at 1 g/kg may be given over 45–60 min. If symptoms are alleviated, a second dose may be given within 3–4 h and a

third dose the next day. Care must be taken to avoid dehydration.

The mechanism of the drug’s benefit against ciguatera poisoning is

unclear but may be due to decreased sodium conductance across

neuronal cell membranes. Hyperosmotic water-drawing action is

another proposed mechanism but no changes in neuronal cell

edema have been observed in vitro. Amitriptyline (25 mg orally

twice a day) reportedly alleviates pruritus and dysesthesias and

may decrease rates of subsequent development of chronic nerve

symptoms. Gabapentin and pregabalin have shown some efficacy in

the treatment of long-term nerve pain in case reports, but evidence

from controlled trials is lacking.

During recovery from ciguatera poisoning, the victim should

exclude the following from the diet for 6 months: fish (fresh or

preserved), fish sauces, shellfish, shellfish sauces, alcoholic beverages, nuts, and nut oils. Consumption of fish in ciguatera-endemic

regions should be avoided.

■ PARALYTIC SHELLFISH POISONING

Paralytic shellfish poisoning is induced by ingestion of filter-feeding

organisms, including clams, oysters, scallops, mussels, chitons, limpets,

starfish, and sand crabs. The most common agent is saxitoxin, produced by dinoflagellates in the genera Alexandrium, Gonyaulax, and

Pyrodinium. These unicellular phytoplankton form the foundation of

the food chain for many filter-feeding organisms and the toxin accumulates in their tissues. In the United States, paralytic shellfish poisoning is acquired primarily from seafood harvested in the Northeast,

the Pacific Northwest, and Alaska. During algal blooms (“red tides”)

in the summer months, these planktonic species can release massive

amounts of toxic metabolites into the water and cause mortality in bird

and marine populations. The paralytic shellfish toxins are water soluble

as well as heat and acid stable; ordinary cooking or freezing does not

destroy them. Contaminated seafood looks, smells, and tastes normal.

Saxitoxin appears to block sodium conductance, inhibiting neuromuscular transmission at the axonal and muscle membrane levels. A toxin

concentration of >75 μg/100 g of foodstuff is considered hazardous

to humans. During an algal bloom, the concentration of saxitoxin in

shellfish can exceed 9000 μg/100 g. A mouse bioassay that identifies

saxitoxin in suspected shellfish is currently in use. Saxitoxin can be

detected in body fluids by high-performance liquid chromatography,

but this method is generally not available in the clinical setting.

TABLE 460-3 Representative Symptoms and Signs of Ciguatera

Poisoning

SYSTEM SYMPTOMS/SIGNS

Gastrointestinal Abdominal pain, nausea, vomiting, diarrhea

Neurologic Paresthesias, pruritus, tongue and throat numbness or

burning, sensation of “carbonation” during swallowing,

odontalgia or dental dysesthesias, dysphagia, tremor,

fasciculations, athetosis, meningismus, aphonia, ataxia,

vertigo, pain and weakness in the lower extremities,

visual blurring, transient blindness, hyporeflexia,

seizures, coma

Dermatologic Conjunctivitis, maculopapular rash, skin vesiculations,

dermographism

Cardiovascular Bradycardia, heart block, hypotension, central

respiratory failurea

Other Chills, dysuria, dyspnea, dyspareunia, fatigue, nasal

congestion and dryness, insomnia, hypersalivation,

diaphoresis, headache, arthralgias, myalgias

a

Tachycardia and hypertension may occur after potentially severe transient

bradycardia and hypotension. Death is rare.

3607 Disorders Caused by Venomous Snakebites and Marine Animal Exposures CHAPTER 460

Intraoral and perioral paresthesia can occur within minutes to a few

hours after ingestion of contaminated shellfish and can progress rapidly to involve the neck and distal extremities. Other neurologic symptoms can include headache, vertigo, ataxia, diffuse muscle weakness,

hyperreflexia, and cranial neuropathies such as dysarthria, dysphagia,

dysphonia, and transient vision loss. Gastrointestinal symptoms can

include nausea, vomiting, diarrhea, and abdominal pain. Flaccid paralysis and respiratory insufficiency may follow 2–12 h after ingestion. In

the absence of hypoxia, the victim often remains alert but paralyzed.

Up to 12% of patients may die.

TREATMENT

Paralytic Shellfish Poisoning

Treatment is supportive and based on symptoms. If the victim

seeks medical attention within the first few hours after ingestion,

activated charcoal (50–100 g) can be administered in the absence

of vomiting. Gastric lavage and cathartics have been attempted

but there is no evidence of benefit and most authors recommend

against their use.

The most serious concern is respiratory paralysis. The victim

should be closely observed for respiratory distress for at least 24 h in

a hospital. With prompt recognition of respiratory failure and establishment of ventilatory support, anoxic myocardial and brain injury

may be prevented. If the patient survives for 18 h, the prognosis is

good for a complete recovery.

■ AMNESIC SHELLFISH POISONING

Amnesic shellfish poisoning occurs when humans consume shellfish

containing domoic acid. Marine diatoms of the genera Nitzschia and

Pseudonitzchia produce the toxin, which can bioaccumulate in filter

feeders during algal blooms. Clams, mussels, oysters, anchovies, and

Dungeness crabs have all been found to cause amnesic shellfish poisoning. Domoic acid is an excitotoxic amino acid capable of binding to

kainate and AMPA-type glutamate receptors in the central nervous system. Uncontrolled calcium influx into neurons stimulated by domoic

acid binding causes neurodegeneration and apoptosis. The toxin is heat

stable and is not affected by cooking or freezing. Shellfish can be tested

for domoic acid by mouse bioassay and high-performance liquid chromatography (HPLC). The regulatory limit for domoic acid in shellfish

is 20 parts per million. An enzyme-linked immunoassay has been

developed to detect domoic acid in human body fluids but is generally

not available in clinical laboratories.

Most victims will report symptoms within 5 h of ingesting contaminated shellfish but delayed onset of up to 40 h has been reported. Symptoms include nausea, vomiting, diarrhea, abdominal cramps, and a

variety of neurologic manifestations, such as severe headache, memory

loss, seizures, hemiparesis, ophthalmoplegia, grimacing, purposeless

chewing, agitation, emotional lability, and coma. Cardiac dysrhythmias,

hypotension, and pulmonary edema have also been reported. Postmortem examination of brain tissue has shown neuronal necrosis or cell loss

and astrocytosis, most prominently in the hippocampus and amygdala.

Several months after the primary intoxication, victims may still display

chronic residual memory deficits and motor or sensory neuropathy.

TREATMENT

Amnesic Shellfish Poisoning

Therapy is supportive and based on symptoms. IV fluids and antiemetics may be used for severe nausea, vomiting, and diarrhea.

Domoic acid neurotoxicity is primarily seizure mediated; anticonvulsive therapy using GABA agonists (e.g., benzodiazepines,

propofol, or barbiturates) should be instituted early. However, some

patients without clinically evident seizure activity have developed

neurologic sequelae.

■ DIARRHETIC SHELLFISH POISONING

Diarrhetic shellfish poisoning occurs with consumption of shellfish

containing the lipophilic compound okadaic acid. This toxin inhibits

serine and threonine protein phosphatases, with consequent protein

accumulation and continued secretion of fluid by intestinal cells leading to diarrhea. Shellfish acquire these toxins by feeding on dinoflagellates, particularly of the genera Dinophysis and Prorocentrum.

Symptoms include diarrhea, nausea, vomiting, abdominal pain, and

chills. Onset typically occurs between 30 min and 12 h after ingestion

of contaminated shellfish. The illness is usually self-limited; most

patients recover in 3–4 days and only a few require hospitalization.

Treatment is supportive and focused on hydration. Toxins can be

detected in food samples by a mouse bioassay, an immunoassay, and

fluorometric HPLC.

Acknowledgment

Kirsten B. Hornbeak and Robert L. Norris contributed to this chapter in

the prior edition and material from that chapter has been retained here.

We would like to dedicate this chapter to the late Dr. Paul S. Auerbach,

who was a contributing author for the previous seven editions of Harrison’s

Principles of Internal Medicine. Dr. Auerbach had a tremendous impact

on the field of emergency medicine and founded the subspecialty of wilderness medicine. Dr. Auerbach was a wonderful teacher, mentor, and

friend, and will be deeply missed.

■ FURTHER READING

Blohm E et al: Marine envenomations, in Goldfrank’s Toxicologic

Emergencies, 11th ed. LS Nelson et al (eds). New York, McGraw-Hill

Education, 2019, pp 1567-1580.

Bush SP et al: Comparison of F(ab’)2 versus Fab antivenom for pit

viper envenomation: A prospective, blinded, multicenter, randomized clinical trial. Clin Toxicol 53:37, 2015.

Cannon R et al: Acute hypersensitivity reactions associated with

administration of crotalidae polyvalent immune Fab antivenom. Ann

Emerg Med 51:407, 2008.

Fil LJ et al: Food Poisoning, in Goldfrank’s Toxicologic Emergencies,

11th ed. LS Nelson et al (eds). New York, McGraw-Hill Education,

2019, pp 592-605.

French LK et al: Marine vertebrates, cnidarians, and mollusks, in

Critical Care Toxicology: diagnosis and management of the critically

poisoned patient, 2nd ed. J Brent et al (eds). New York, Springer, 2017,

pp 2045-2074.

Green S: Ciguatera, in Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient, 2nd ed. J Brent et al (eds). New

York, Springer, 2017, pp 2033-2043.

Hornbeak KB, Auerbach PS: Marine envenomation. Emerg Med

Clin North Am 35:321, 2017.

Kang AM, Fisher ES: Thromboelastography with platelet studies

(TEG® with PlateletMapping®) after rattlesnake envenomation in

the southwestern United States demonstrates inhibition of ADPinduced platelet activation as well as clot lysis. J Med Toxicol 16:24,

2020.

Lavonas EJ et al: Unified treatment algorithm for the management

of crotaline snakebite in the United States: results of an evidenceinformed consensus workshop. BMC Emerg Med 11:2, 2011.

Longbottom J et al: Vulnerability to snakebite envenoming: A global

mapping of hotspots. Lancet 392:673, 2018.

Ruha A et al: Native (US) venomous snakes and lizards, in Goldfrank’s

Toxicologic Emergencies, 11th ed. LS Nelson et al (eds). New York,

McGraw-Hill Education, 2019, pp 1617-1626.

Suguitan MA et al: Scombroid, in Critical Care Toxicology: Diagnosis

and Management of the Critically Poisoned Patient, 2nd ed. J Brent

et al (eds). New York, Springer, 2017, pp 2075-2083.

World Health Organization: Snakebite envenoming−A strategy for prevention and control. Available from https://www.who.

int/snakebites/resources/9789241515641/en/. Accessed May 11,

2020.

3608 PART 14 Poisoning, Drug Overdose, and Envenomation

Ectoparasites include arthropods and creatures from other phyla that

infest the skin or hair of animals; the host animals provide them with

sustenance and shelter. The ectoparasites may remain superficially on

the skin or hair, attached by mouthparts and specialized claws. Other

ectoparasites may penetrate the skin and reside in the epidermis, dermis, or subcutis. Ectoparasites may inflict direct mechanical injury, consume blood or nutrients, induce hypersensitivity reactions, inoculate

toxins, transmit pathogens, create openings in the skin for secondary

bacterial infection, and incite fear or disgust. Human beings are the sole

or obligate hosts for only a few kinds of ectoparasites but serve as facultative, dead-end, or paratenic (accidental) hosts for many others. Of

the organisms discussed in this chapter, only scabies mites (the hominis

variety) and human-infesting lice are obligate parasites of humans.

Arthropods that are capable of ectoparasitism or that can otherwise

cause injury include insects (such as lice, fleas, bed bugs, wasps, ants,

bees, and diverse kinds of flies), arachnids (spiders, scorpions, mites,

and ticks), and myriapods (millipedes and centipedes). Several arthropods can cause uncomfortable reactions when they or their setae and

exudates contact skin, mucous membranes, and ocular tissues.

Certain nematodes (helminths), such as the hookworms (Chap. 231),

are ectoparasitic in that they penetrate and migrate through the skin.

Infrequently encountered ectoparasites in other phyla include the pentastomes (armillifers or tongue worms) and leeches.

Arthropods may cause injury when they attempt to take a blood meal

or as they defend themselves by biting, stinging, or exuding venoms.

Papular urticaria and other lesions caused by arthropod bites and stings

are so diverse and variable (depending upon the host’s health status and

prior exposure to the arthropod’s saliva, venom, or other exudates) that

it is difficult to identify the precise causative organism without a bona

fide specimen and taxonomic expertise. Specimens of the presumably

offending arthropod should, whenever possible, be sampled (ideally by

medical personnel) directly (when taken from the patient) or indirectly

by the use of traps or other monitoring devices in the patient’s home

or workplace. Samples sent to laboratorians for evaluation should be

properly fixed, preserved, and packaged. Information on the patient’s

travel history, occupation and avocation, and exposure to animals—pets

and pests—often helps the clinician and parasitologist resolve the cause.

■ SCABIES

The human itch mite, Sarcoptes scabiei var. hominis, is an obligate

human ectoparasite and a common cause of itchy dermatosis, affecting

~250 million persons worldwide. Gravid female mites (~0.3 mm in

length) burrow superficially within the stratum corneum, depositing

several eggs per day. Six-legged larvae mature to eight-legged nymphs

and then to adults. Gravid adult females emerge to the surface of the

skin about 8 days later and then (re)invade the skin of the same or

another host. Newly fertilized female mites are transferred from person

to person mainly by direct skin-to-skin contact; transfer is facilitated

by crowding, poor hygiene, and close physical contact with other

persons. Generally, scabies mites die within a day or so in the absence

of a suitable host. Transmission via sharing of contaminated bedding or

clothing occurs less frequently than is often thought. In the United States,

scabies may account for up to 5% of visits to dermatologists. Outbreaks

are known to occur in preschools, hospitals, nursing homes, prisons,

and other institutional residences.

The itching and rash associated with scabies derive from a sensitization reaction to mites and their secretions/excretions. A person’s

initial infestation typically remains asymptomatic for up to 6 weeks

before the onset of intense pruritus, but a reinfestation produces a

hypersensitivity reaction without delay. Burrows become surrounded

by inflammatory infiltrates composed of eosinophils, lymphocytes, and

461 Ectoparasite Infestations

and Arthropod Injuries

Richard J. Pollack, Scott A. Norton

histiocytes. Infested individuals often feel generalized pruritus, not just

in the most heavily involved areas. Hyperinfestation with thousands of

mites, a condition known as crusted scabies (formerly termed Norwegian scabies), may result from glucocorticoid use, immunodeficiency

(including that due to HIV/AIDS), and neurologic or psychiatric illnesses that limit the itch and/or the scratch response.

Pruritus typically intensifies at night and after hot showers. Classic

burrows are often difficult to find because they are few in number and

may be obscured by excoriations. Burrows appear as dark wavy lines

in the upper epidermis and are 3–15 mm long. Scabietic lesions are

most common on the volar wrists and along the digital web spaces.

In males, the penis and scrotum almost invariably become involved.

Small papules and vesicles, often accompanied by eczematous plaques,

pustules, or nodules, appear symmetrically at those sites and within

intertriginous areas, around the navel and belt line, in the axillae, and

on the buttocks and upper thighs. Except in infants, the face, scalp,

neck, palms, and soles are usually spared. Crusted scabies often resembles psoriasis: both are characterized by widespread thick keratotic

crusts, scaly plaques, and dystrophic nails. Characteristic burrows are

not seen in crusted scabies, and patients usually do not itch, although

their infestations are highly contagious and have been responsible for

outbreaks of common scabies in hospitals.

Scabies should be considered in patients with pruritus and symmetric superficial, excoriated, papulovesicular skin lesions in characteristic locations, particularly if there is a history of direct and

prolonged contact with an infested person. Burrows should be sought

and unroofed with a sterile needle or scalpel blade, and the scrapings

should be examined microscopically for mites, eggs, and fecal pellets.

Examination of biopsied skin samples (including those obtained by

superficial cyanoacrylate biopsy) or scrapings, dermatoscopic imaging

of papulovesicular lesions, and microscopic inspection of clear cellophane tape lifted from lesions also may be diagnostic. In the absence

of identifiable mites or eggs, a clinical diagnosis is based on a history

of pruritus, a physical examination, and an epidemiologic link. Unrelated skin diseases are frequently misdiagnosed as scabies, particularly

in presumed “outbreak” situations. Sarcoptes mites of other mammals

may cause transient irritation, but they do not reside or reproduce in

human hosts. In some aboriginal communities, household dogs may

serve as reservoirs for human scabies mites.

TREATMENT

Scabies

The four scabicides approved by the U.S. Food and Drug Administration (FDA)—permethrin, crotamiton, spinosad, and lindane—

are topical and available solely by prescription. Permethrin cream

(5%) is less toxic than 1% lindane preparations and is effective

against lindane-resistant infestations. Scabicides are applied thinly

but thoroughly from the jawline down after bathing, with careful

application to interdigital spaces, the navel, and under the nails,

and are removed 6–14 h later with soap and water. Treatment of

crusted scabies is difficult and may require preapplication of a keratolytic agent such as 6% salicylic acid and then of scabicides to the

skin’s entire surface, including the scalp, face, and ears. Repeated

treatments or the sequential use of several agents may be necessary.

Ivermectin, which is approved by the FDA for the treatment of two

nematodal diseases, has not been approved for the treatment of scabies; however, a single oral dose (200 μg/kg) is effective in otherwise

healthy persons. Patients with crusted scabies require three to seven

doses of ivermectin over 8–30 days, along with topical permethrin

and possibly a keratolytic compound.

Within 1 day of effective treatment, scabies infestations become

noncommunicable, but the pruritic hypersensitivity dermatitis

induced by dead mites and their detritus frequently persists for

weeks. Unnecessary retreatment with topical agents may provoke

contact dermatitis, especially from repeated applications of permethrin cream. Topical emollients, menthol and methyl salicylate

products, calamine lotion, and oral antihistamines relieve itching

3609Ectoparasite Infestations and Arthropod Injuries CHAPTER 461

during treatment. Topical glucocorticoids may calm pruritus that

lingers after effective treatment. To prevent reinfestations, bedding

and clothing should be washed and dried on high heat or heatpressed, and other environmental surfaces or fomites should be

cleaned. Close contacts of confirmed cases, even if asymptomatic,

should be treated simultaneously.

Scabies infestations often lead to secondary bacterial infections,

usually with Staphylococcus aureus or Streptococcus pyogenes (or

both). Consequences of these superinfections include impetigo,

cellulitis, invasive bacterial infections, poststreptococcal glomerulonephritis, and possibly acute rheumatic fever.

■ CHIGGERS AND OTHER BITING MITES

Chiggers are the larvae of trombiculid (harvest) mites that normally

feed on mice and other small vertebrates in grassy or brush-covered

sites in tropical, subtropical, and (less frequently) temperate areas

during warm months. They reside on low vegetation and attach themselves to passing vertebrate hosts. While feeding, larvae secrete saliva

with proteolytic enzymes to create a tube-like invagination in the host’s

skin; this stylostome allows the mite to imbibe tissue fluids. The saliva

is highly antigenic and causes small (usually <1 cm in diameter) but

exceptionally pruritic papular, urticarial, or pustulovesicular lesions. In

persons previously sensitized to salivary antigens, the papules develop

within hours of attachment. While attached, mites appear as minute

(~0.5-mm diameter) red dots on the skin. Generally, lesions have a

hemorrhagic base and are slightly elevated, resembling vasculitic papules. Scratching invariably destroys the body of a mite, but itching and

burning often persist for weeks. The rash is common on the ankles and

in areas where circumferentially tight clothing obstructs the further

wanderings of the mites. Repellents are useful for preventing chigger

bites. Chiggers (Leptotrombidium species) serve as vectors for Orientia

tsutsugamushi, the agent of scrub typhus in the eastern half of Asia

and the Indomalayan and Australasian regions. Endemic foci of scrub

typhus were recently identified in southern Chile and in East Africa, far

outside the traditional endemic region.

Many kinds of mites associated with peridomestic birds and rodents

are particularly bothersome when they invade homes and bite people.

In North America, the northern fowl mite, chicken mite, tropical rat

mite, and house mouse mite normally feed on poultry, other birds,

and small mammals. After their natural hosts leave the nest or die, the

mites disperse and may invade homes. Although the mites are rarely

seen because of their small size, their bites can be painful and pruritic.

House mouse mites (Liponyssoides sanguineus) serve as vectors for the

agent of rickettsialpox, Rickettsia akari, an uncommon disease characterized by mild fevers, an eschar at the bite site, and a papulovesicular

eruption. Rickettsialpox (Chap. 187) has been recognized mainly in

large northern temperate cities. Once confirmed as the cause of a skin

disorder, rodent- and bird-associated mites are best eliminated by

exclusion of their animal hosts, removal of the nests, and cleaning and

treatment of the nesting area with appropriate acaricides.

Pyemotes and other mites that infest grain, straw, cheese, hay, oak

leaf galls, or other products occasionally produce similar episodes of

rash and discomfort and may produce a unique dermatologic “comet

sign” lesion—a paisley-shaped urticarial plaque (Fig. 461-1).

Diagnosis of mite-induced dermatitides (including those caused by

chiggers) relies on confirmation of the mite’s identity or elicitation of a

history of exposure to the mite’s source. Because the mites do not reside

on humans, treatment of the patient with acaricides (e.g., permethrin)

is discouraged. Oral antihistamines or topical steroids may reduce

mite-induced pruritus temporarily.

The mites that cause house dust–related allergic conditions neither

bite nor infest humans.

■ TICK BITES AND TICK PARALYSIS

Ticks attach superficially to skin and usually feed painlessly; blood

is their only food. Their salivary secretions are biologically active

(intended to prevent blood coagulation while the tick feeds) and can

produce local reactions, induce fevers, and cause paralysis in addition

to transmitting diverse pathogens. The two main families of ticks are

the hard (ixodid) ticks and soft (argasid) ticks. Because no ticks are

obligate parasites on humans, all tick-borne diseases (bacterial, viral,

and protozoal) are zoonoses.

Generally, soft ticks feed quickly, attaching for <1 h, and then drop

off. Because of this rapid feeding behavior, the ticks are not carried

widely by animal or bird hosts. Soft tick–associated infections usually

have fairly focal distributions. When a soft tick finishes the blood meal

on a human and drops off, red macules may develop at the bite site.

Some species in Africa, the western United States, and Mexico produce

painful hemorrhagic lesions.

Hard ticks are much more common than are soft ticks, and

they transmit most of the tick-borne infections that are familiar to

physicians and patients. Hard ticks attach to the host and feed for

several days to >1 week, with the exact duration depending upon

the tick’s species and stage of development. At the site of hard-tick

bites, small areas of induration, often purpuric, develop and may be

surrounded by an erythematous rim. A necrotic eschar, called a tâche

noire (“black spot”), occasionally develops. Chronic nodules (persistent tick-bite granulomas) can be several centimeters in diameter

and may linger for months after the feeding tick has been removed.

These granulomas can be treated with injected intralesional glucocorticoids or by simple local excision. Tick-induced fever, unassociated with transmission of any pathogen, is often accompanied by

headache, nausea, and malaise but usually resolves ≤36 h after the

tick is removed. Salivary antigens of certain ticks, particularly the

Lone Star tick, Amblyomma americanum, may induce antibodies to

galactose-α-1,3-galactose (alpha-gal) that result in mammalian meat

allergy–alpha-gal syndrome.

Tick paralysis, an acute ascending flaccid paralysis that resembles

Guillain-Barré syndrome, is believed to be caused by one or more toxins in tick saliva that block neuromuscular transmission and decrease

nerve conduction. This rare complication has followed the bites of >60

species of ticks. It is reported worldwide, but most cases arise in the

Rocky Mountain region, in the northwestern United States and southeastern Canada, and on the east coast of Australia. In North America, dog

and wood ticks (Dermacentor species) are most commonly involved.

Weakness begins symmetrically in the lower extremities ≤6 days after

the tick’s attachment, ascends symmetrically during several days, and

may culminate in complete paralysis of the extremities and cranial

nerves. Deep tendon reflexes are diminished or absent, but sensory

examination and findings on lumbar puncture are typically normal.

Diagnosis depends on finding the tick, which is often hidden beneath

scalp hair. Removal of the tick generally leads to improvement within

a few hours and complete recovery after several days, although the

patient’s condition may continue to deteriorate for a full day. Failure

to remove the tick may lead to dysarthria, dysphagia, and ultimately

death from aspiration or respiratory paralysis. An antiserum to the

saliva of Ixodes holocyclus, the usual cause of tick paralysis in Australia,

effectively reverses paralysis caused by these ticks.

Removal of hard ticks during the first 36 h of attachment generally prevents transmission of the agents of Lyme disease, babesiosis,

anaplasmosis, and ehrlichiosis, although tick-borne viruses may be

transmitted more quickly. Ticks should be removed by traction with

fine-tipped forceps placed firmly around the tick’s mouthparts where

they enter the skin. Careful handling (to avoid rupture of ticks) and

use of gloves may avert accidental contamination with pathogens

contained in tick fluids. Use of occlusive dressings, heat, or various

substances (in an attempt to induce the tick to detach) merely delays

tick removal. Afterward, the site of attachment should be disinfected.

Tick mouthparts sometimes remain in the skin but generally are shed

spontaneously within days without the need for surgical removal. Current guidelines from the Centers for Disease Control and Prevention

suggest that, rather than awaiting the onset of erythema migrans, the

results of tick testing, or seroconversion to antigens diagnostic for

Lyme disease, physicians may appropriately administer prophylaxis—a

single oral dose of doxycycline (200 mg) within 72 h of tick removal—

to adult patients with bites thought to be associated with Ixodes scapularis

(deer ticks) in Lyme disease–endemic areas. Whereas prophylactic

3610 PART 14 Poisoning, Drug Overdose, and Envenomation

antibiotic treatment may have value in preventing Lyme disease, it is

not recommended as a means to prevent other tick-borne infections.

The Asian longhorned tick (Haemaphysalis longicornis) is a newly

invasive species in the United States, first detected in the northeastern

states in 2017. Although it carries several pathogens to domestic animals, wildlife, and humans in its natural range (northeastern Asia), it

has not yet been implicated in disease transmission in the United States.

■ LOUSE INFESTATION (PEDICULIASIS AND PTHIRIASIS)

Three kinds of biting lice are obligate blood-feeding ectoparasites

of human beings. These include the human head and body lice that

represent distinct genetic clades of Pediculus humanus, and the pubic

(“crab”) lice (Pthirus pubis). Nymphs and adults of these lice feed at

least once a day, ingesting human blood exclusively, and they partition

ecologically on the host. Head lice infest mainly the hair of the scalp,

body lice the clothing, and pubic lice mainly the hair of the pubis. The

saliva of lice produces a pruritic morbilliform or urticarial rash in some

sensitized persons. Female head and pubic lice cement their eggs (nits)

firmly to hair, whereas female body lice cement their eggs to clothing,

particularly to threads along clothing seams. After ~10 days of development within the egg, a nymph emerges. Empty eggs may remain affixed

for months or years thereafter.

Body lice are acquired by direct contact with an infested person

or that individual’s recently used clothing or bedding. These lice

venture for just minutes to the skin to feed, but otherwise sequester on

clothing. They generally succumb in ≤2 days if separated from their

host. Body lice tend to be limited to a small proportion of indigent

persons or others who have relevant exposure and lack the wherewithal or desire to change or appropriately launder their clothing

and bedding. Body lice, as well as the pathogens they transmit, may

become increasingly prevalent after societal upheaval and disasters.

These lice are vectors for the agents of louse-borne (epidemic) typhus

(Chap. 187), louse-borne relapsing fever (Chap. 185), and trench

fever (Chap. 172). Chronic infestations result in a postinflammatory

hyperpigmentation and thickening of the skin known as vagabond’s

disease.

Head lice are acquired mainly by direct head-to-head contact rather

than via fomites such as shared headgear, bed linens, and grooming

implements. The prevalence of head lice varies widely as a function of

age, geography, and cultural habits. In North America, the prevalence

is greatest (~1%) among 6- to 10-year-old children and is considerably

lower among persons of other ages. Infestations can be far more prevalent elsewhere. Generally, an infested person hosts 10 or fewer head

lice. Chronically infested persons tend to be asymptomatic, and some

may host >100 lice. Pruritus, due mainly to hypersensitivity to the

louse’s saliva, usually is transient and mild and is most evident around

the posterior hairline. Head lice removed from a person succumb to

desiccation and starvation within ~1 day. Head lice are generally considered unimportant as natural vectors for any pathogens.

FIGURE 461-1 Comet signs in individuals with known or suspected mite-bite reactions, likely due to Pyemotes species. Note central punctum at bite site, surrounded by

edematous erythema. Linear or serpiginous “comet tails” emanate from the central site. Pyemotes-induced comet tails generally do not follow typical patterns of ascending

lymphatic drainage.

3611Ectoparasite Infestations and Arthropod Injuries CHAPTER 461

The crab or pubic louse is transmitted mainly by sexual contact.

These lice occur predominantly on pubic hair and less frequently on

axillary or facial hair, including the eyelashes. Children and adults

may acquire pubic lice by sexual or close nonsexual contact. Intensely

pruritic, bluish macules ~3 mm in diameter (maculae ceruleae) develop

at the site of bites. Blepharitis commonly accompanies infestations of

the eyelashes.

Pediculiasis is often suspected upon the detection of presumed nits

firmly cemented to hairs or in clothing or on the basis of pruritus.

Often, objects presumed to be louse eggs are, instead, pseudo-nits

composed of debris and hair-associated fungi. Hatched and dead

eggs remain firmly affixed to scalp hair for months. Such relicts are

frequently misconstrued to be signs of an active louse infestation.

Confirmation of a louse infestation, therefore, should rely on the discovery of a live louse.

TREATMENT

Louse Infestation

Body lice usually are eliminated by bathing and by changing to

laundered clothes. Application of topical pediculicides from head to

foot may be necessary for hirsute patients. Clothes and bedding are

effectively deloused by heating in a clothes dryer at ≥55°C (≥131°F)

for 30 min or by heat-pressing. Emergency mass delousing of persons and clothing may be warranted during periods of civil strife

and after natural disasters to reduce the risk of pathogen transmission by body lice.

Head lice and their eggs may be removed with a fine-toothed

louse or nit comb, but this effort can be difficult and timeconsuming and often fails to eradicate the lice. Treatment of newly

identified, active infestations traditionally relies on a 10-min topical application of ~1% permethrin or pyrethrins, with a second

application ~10 days later. Lice persisting after this treatment may

be resistant to pyrethroids. Chronic infestations may be treated for

≤12 h with 0.5% malathion. Lindane is applied for just 4 min but

seems less effective and may pose a greater risk of adverse reactions,

particularly when misused. Resistance of head lice to permethrin,

malathion, and lindane is well documented. Newer FDA-approved

topical pediculicides contain benzyl alcohol, dimethicone, spinosad,

and ivermectin. Although children infested by head lice—or those

who simply have remnant nits from a prior infestation—are frequently isolated or excluded from school, this practice increasingly

is considered to be unjustified, ineffective, and counterproductive.

Pubic louse infestations are treated with topical pediculicides,

except for eyelid infestations (pthiriasis palpebrum), which generally respond to a coating of petrolatum applied for 3–4 days.

■ MYIASIS (FLY INFESTATION)

Myiasis refers to infestations by fly larvae (maggots) that invade living

or necrotic tissues or body cavities and produce different clinical syndromes, depending on the species of fly.

In forested parts of Central and South America, larvae of the human

botfly (Dermatobia hominis) produce furuncular (boil-like) dermal

and subcutaneous nodules ≤3 cm in diameter. A gravid adult female

botfly captures a mosquito or another bloodsucking insect and deposits her eggs on its abdomen. When the carrier insect attacks a human or

another mammalian host (often cattle) several days later, the warmth

and moisture of the host’s skin stimulate the eggs to hatch. The emerging larvae, ~1 mm long, promptly penetrate intact skin. After 6–12 weeks

of development, mature larvae emerge from the skin and drop to the

ground to pupate and then become adults.

The African tumbu fly (Cordylobia anthropophaga) deposits its

eggs on damp sand, leaf litter, or drying laundry, particularly items

contaminated by urine or sweat. Larvae hatch from eggs upon contact

with a host’s body and penetrate the skin, producing boil-like lesions

from which mature larvae emerge ~9–10 days later. Furuncular myiasis

is suggested by uncomfortable lesions with a central breathing pore

that emit bubbles when submerged in water. A sensation of movement

under the patient’s skin may cause severe emotional distress.

Larvae that cause furuncular myiasis may be induced to emerge if

the air pore is coated with petrolatum or another occlusive substance.

Removal may be facilitated by injection of a local anesthetic (or sterile

injectable saline) into the subjacent tissue to uplift the larva through

the breathing pore. Surgical excision is sometimes necessary because

upward-pointing spines of some species hold the larvae firmly in place.

Other fly larvae cause nonfuruncular myiasis. Larvae of the horse

botfly (Gasterophilus intestinalis) emerge from eggs, usually deposited on the hairs of a horse’s front legs. Direct contact with a person’s

bare hands or legs may result in the larvae’s hatching from the eggs

and invading skin. After penetrating human skin, these larvae rarely

mature but instead may migrate for weeks in the dermis. The resulting

pruritic and serpiginous eruption resembles cutaneous larva migrans

caused by canine or feline hookworms (Chap. 231). Larvae of rabbit

and rodent botflies (Cuterebra species) occasionally cause cutaneous

or tracheopulmonary myiasis.

Certain flies are attracted to blood and pus, laying their eggs on

open or draining sores. Newly hatched larvae enter wounds or diseased

skin. Larvae of several types of green bottle flies (Lucilia species) usually remain superficial and confined to necrotic tissue. Specially raised,

sterile “surgical maggots” are sometimes used deliberately for wound

debridement. Larvae of screwworm flies (Cochliomyia) and flesh flies

(Wohlfahrtia species) invade viable tissues more deeply and produce

large suppurating lesions. Larvae that infest wounds also may enter

body cavities such as the mouth, nose, ears, sinuses, anus, vagina, and

lower urinary tract, particularly in unconscious or otherwise debilitated patients. The consequences range from harmless colonization to

destruction of the nose, meningitis, and deafness. Treatment involves

removal of maggots and debridement of tissue.

Larvae of the sheep botfly, Oestrus ovis, and other flies responsible

for furuncular and wound myiasis also may cause ophthalmomyiasis. Sequelae include nodules in the eyelid, retinal detachment, and

destruction of the globe. Most instances in which maggots are found in

human feces result from deposition of eggs or larvae by flies on recently

passed stools, not from an intestinal maggot infestation.

■ PENTASTOMIASIS

Pentastomids (tongue worms), an obscure type of crustacean, inhabit

the respiratory passages of reptiles and carnivorous mammals. Human

infestation by Linguatula serrata is common in the Middle East and

results from the consumption of encysted larval stages in raw liver or

lymph nodes of sheep and goats, which are true intermediate hosts for

the tongue worms. In areas where raw sheep and goat liver are served,

larvae migrate to the nasopharynx and produce an acute self-limiting

syndrome—known as halzoun in Lebanon and marrara in Sudan—

characterized by rapid onset (within <12 h) of pain and itching of the

throat and ears, coughing, hoarseness, dysphagia, and dyspnea. Severe

edema may cause obstruction that requires tracheostomy. In addition,

ocular invasion has been described. Diagnostic larvae measuring ≤10 mm

in length appear in copious nasal discharge or vomitus.

Another type of tongue worm, Armillifer armillatus, infects people

who consume its eggs in contaminated food or drink or after handling

the definitive host, the African python. Larvae encyst in various organs,

usually the liver or peritoneum, but rarely cause symptoms. Cysts

may require surgical removal as they enlarge during worm molting,

but they usually are encountered as an incidental finding at autopsy.

Parasite-induced lesions may be misinterpreted as a malignancy, with

the correct diagnosis confirmed histopathologically. Cutaneous larva

migrans–type syndromes of other pentastomes have been reported

from Southeast Asia and Central America.

■ LEECH INFESTATIONS

Medically important leeches are annelid worms that attach to their

hosts with chitinous cutting jaws and draw blood through muscular

suckers. Medicinal leeches (Europe: Hirudo medicinalis and other

Hirudo species; Asia: Hirudinaria manillensis; North America: Macrobdella

3612 PART 14 Poisoning, Drug Overdose, and Envenomation

decora) are still used occasionally for medical purposes to reduce

venous congestion in surgical flaps or replanted body parts. This practice has been complicated by intractable bleeding, wound infections,

myonecrosis, and sepsis due to Aeromonas hydrophila, which colonizes

the gullets of commercially available leeches.

Ubiquitous aquatic leeches that parasitize fish, frogs, and turtles

readily attach to human skin—most often the nasal mucosa—and

avidly suck blood. Attachment is usually painless, and the leeches will

detach themselves when satiated with a blood meal. Hirudin, a powerful anticoagulant secreted by the leech, causes continued bleeding

after the leech has detached. Healing of a leech-bite wound is slow,

and secondary bacterial infections are not uncommon. Several kinds

of aquatic leeches in Africa, Asia, and southern Europe can enter the

mouth, nose, and genitourinary tract and attach to mucosal surfaces

at sites as deep as the esophagus and trachea. Leeches may detach on

exposure to gargled saline or may be removed by forceps or medical

suction.

Arboreal land leeches, which live amid rain forest vegetation, are

attracted by heat and can drop from a leaf onto one’s skin. Externally

attached leeches generally drop off after they have engorged, but

removal is hastened by gentle scraping aside of the anterior and posterior suckers the leech uses for attachment and feeding. Some authorities dispute the wisdom of removing leeches with alcohol, salt, vinegar,

insect repellent, a flame or heated instrument, or applications of other

noxious substances.

■ SPIDER BITES

Of the >30,000 recognized species of spiders, only ~100 defend themselves aggressively and have fangs sufficiently long to penetrate human

skin. The venom that some spiders use to immobilize and digest their

prey can cause necrosis of the skin and systemic toxicity. Whereas the

bites of most spiders may be painful but not harmful, envenomations

by recluse or fiddleback spiders (Loxosceles species) and widow spiders

(Latrodectus species) may be life-threatening. Identification of the

offending spider is important because specific treatments exist for bites

of widow spiders. Except when the patient actually observes a spider

immediately associated with the bite or fleeing from the site, painful

noduloulcerative and other lesions reported as spider-bite reactions are

most often due to other injuries or to infections with bacteria, particularly methicillin-resistant S. aureus (MRSA).

Recluse Spider Bites and Necrotic Arachnidism Brown

recluse spiders (Loxosceles reclusa) live mainly in the southcentral

United States and have close relatives in Central and South America,

Africa, the Mediterranean basin, and the Middle East. Recluse spiders are not aggressive toward humans and bite only if threatened or

pressed against the skin. They generally dwell beneath rocks and logs

or in caves and animal burrows. They invade homes and seek dark and

undisturbed hiding spots in closets, garages, crawl spaces, and attics;

under furniture and rubbish in storage rooms; and in folds of clothing. Despite their impressive abundance in some homes, these spiders

rarely bite humans. Bites tend to occur while the victim is donning

clothing in which the spider has hidden itself and are sustained primarily on the hands, arms, neck, and lower abdomen.

Whereas a bite by a brown recluse spider may cause minor injury

with edema and erythema, envenomation can cause severe necrosis

of skin and subcutaneous tissue and, more rarely, systemic hemolysis. Initially, the bite is painless or may produce a stinging sensation.

Within a few hours, the site becomes painful and pruritic, with central

induration surrounded by a pale ischemic zone that itself is encircled

by a zone of erythema. In most cases, the lesion resolves without

treatment in just a few days. In severe cases, the erythema spreads,

and the center of the lesion becomes hemorrhagic or necrotic with an

overlying bulla. A black eschar forms and sloughs several weeks later,

leaving an ulcer that eventually may create a depressed scar. Healing

usually takes place in ≤3 months. Local complications include injury

to nerves and secondary bacterial infection. Fever, chills, weakness,

headache, nausea, vomiting, myalgia, arthralgia, morbilliform eruption, and leukocytosis may develop ≤72 h after the bite. Reports of

deaths attributed to bites of North American brown recluse spiders

have not been verified.

The Mediterranean recluse spider (Loxosceles rufescens) is a widely

invasive species in urban areas of both the Old and New Worlds. The

dorsal surfaces of L. rufescens and L. reclusa are adorned with a

fiddle-shaped pattern. L. rufescens is warier than L. reclusa, is less likely

to bite, and rarely causes necrosis. Misidentification of this spider may

create spurious reports of L. reclusa activity outside the known range

of that species.

TREATMENT

Recluse Spider Bites

Initial management includes rest, ice, compression, and elevation

(RICE). Analgesics, antihistamines, antibiotics, and tetanus prophylaxis should be administered if indicated. Early debridement

or surgical excision of the wound without closure delays healing.

Routine use of antibiotics or dapsone lacks utility. Patients should

be monitored closely for signs of hemolysis, renal failure, and other

systemic complications.

Widow Spider Bites The black widow spider, common in the

southeastern United States, measures ≤1 cm in body length and 5 cm

in leg span and is shiny black with a red hourglass marking on the ventral abdomen. Other dangerous Latrodectus species occur elsewhere in

temperate and subtropical parts of the world. The bites of the female

widow spiders are notorious for their potent neurotoxins.

Widow spiders spin their webs under stones, logs, plants, or rock

piles and in dark spaces in barns, garages, and outhouses. Bites are

most common in the summer and early autumn and occur when a web

is disturbed or a spider is trapped or provoked. The initial bite is perceived as a sharp pinprick or may go unnoticed. Fang-puncture marks

are uncommon. The venom that is injected does not produce local

necrosis, and some persons experience no other symptoms.

α-Latrotoxin, the most active component of the venom, binds irreversibly to presynaptic nerve terminals and causes release and eventual

depletion of acetylcholine, norepinephrine, and other neurotransmitters from those terminals. Painful cramps may spread within 60 min

from the bite site to large muscles of the extremities and trunk. Extreme

rigidity of the abdominal muscles and excruciating pain may suggest

peritonitis, but the abdomen is not tender on palpation and surgery is

not warranted. The pain begins to subside during the first 12 h but may

recur during several days or weeks before resolving spontaneously. A

wide range of other sequelae may include salivation, diaphoresis, vomiting, hypertension, tachycardia, labored breathing, anxiety, headache,

weakness, fasciculations, paresthesia, hyperreflexia, urinary retention,

uterine contractions, and premature labor. Rhabdomyolysis and renal

failure have been reported, and respiratory arrest, cerebral hemorrhage,

or cardiac failure may end fatally, especially in very young, elderly, or

debilitated persons.

TREATMENT

Widow Spider Bites

Treatment consists of RICE and tetanus prophylaxis. Hypertension

that does not respond to analgesics and antispasmodics (e.g., benzodiazepines or methocarbamol) requires specific antihypertensive

medication. The efficacy and safety of antivenin (i.e., antivenom)

made from equine immunoglobulins are controversial for bites of

the black widow and the closely related Australian redback spider

because of concerns about potential anaphylaxis or serum sickness.

Antivenins made from monoclonal antibodies are in development.

Tarantulas and Other Spiders Tarantulas are large hairy spiders

of which 30 species are found in the United States, mainly in the Southwest.

Several species of tarantulas that have become popular household pets

are usually imported from Central or South America. Tarantulas bite

persons only when threatened and usually cause no more harm than a

3613Ectoparasite Infestations and Arthropod Injuries CHAPTER 461

bee sting, but on occasion, the venom causes deep pain and swelling.

Several species of tarantulas are covered with urticating hairs that are

brushed off in the thousands when a threatened spider rubs its hind

legs across its dorsal abdomen. These hairs can penetrate human skin

and produce pruritic papules that may persist for weeks. Failure to wear

gloves or to wash the hands after handling the Chilean Rose tarantula, a

popular pet spider, has resulted in transfer of hairs to the eye with subsequent devastating ocular inflammation. Treatment of bites includes

local washing and elevation of the bitten area, tetanus prophylaxis, and

analgesic administration. Antihistamines and topical or systemic glucocorticoids are given for exposure to urticating hairs.

Atrax robustus, a funnel-web spider of Australia, and Phoneutria

species, the South American banana spiders, are among the most

dangerous spiders in the world because of their aggressive behavior

and potent neurotoxins. Envenomation by A. robustus causes a rapidly

progressive neuromotor syndrome that can be fatal within 2 h. The bite

of a banana spider causes severe local pain followed by profound systemic symptoms and respiratory paralysis that can lead to death within

2–6 h. Specific antivenins for use after bites by each of these spiders are

available. Yellow sac spiders (Cheiracanthium species) are common in

homes worldwide. Their bites, though painful, generally lead to only

minor erythema, edema, and pruritus.

■ SCORPION STINGS

Scorpions are arachnids that feed on arthropods and other small

animals. They paralyze their prey and defend themselves by injecting venom from a stinger on the tip of the tail. Painful but relatively

harmless scorpion stings need to be distinguished from the potentially

lethal envenomations that are produced by ~30 of the ~1000 known

species and that cause >5000 deaths worldwide each year. Scorpions

are nocturnal and remain hidden during the day in crevices or burrows

or under wood, loose bark, or rocks. They occasionally enter houses

and tents and may hide in shoes, clothing, or bedding. Scorpions sting

humans only when threatened.

Of the 40 or so scorpion species in the United States, only bark

scorpions (Centruroides sculpturatus/C. exilicauda) in the Southwest

produce venom that is potentially lethal to humans. This venom

contains neurotoxins that cause sodium channels to remain open.

Such envenomations usually are associated with little swelling, but

prominent pain, paresthesia, and hyperesthesia can be accentuated by

tapping on the affected area (the tap test). These symptoms soon spread

to other locations; dysfunction of cranial nerves and hyperexcitability

of skeletal muscles develop within hours. Patients present with restlessness, blurred vision, abnormal eye movements, profuse salivation,

lacrimation, rhinorrhea, slurred speech, difficulty in handling secretions, diaphoresis, nausea, and vomiting. Muscle twitching, jerking,

and shaking may be mistaken for a seizure. Complications include

tachycardia, arrhythmias, hypertension, hyperthermia, rhabdomyolysis, and acidosis. Symptoms progress to maximal severity in ~5 h and

subside within a day or two, although pain and paresthesia can last for

weeks. Fatal respiratory arrest is most common among young children

and the elderly.

Envenomations by Leiurus quinquestriatus in the Middle East and

North Africa, by Mesobuthus tamulus in India, by Androctonus species

along the Mediterranean littoral and in North Africa and the Middle

East, and by Tityus serrulatus in Brazil cause massive release of endogenous catecholamines with hypertensive crises, arrhythmias, pulmonary

edema, and myocardial damage. Acute pancreatitis occurs with stings

of Tityus trinitatis in Trinidad, and central nervous toxicity complicates

stings of Parabuthus and Buthotus scorpions of South Africa.

In Iran and adjacent countries, Hemiscorpius lepturus causes the

most scorpion envenomations. Its stings are relatively asymptomatic at

first, but its cytotoxic venom causes pain, hemolysis, and tissue necrosis after the first day. Systemic complications include hemoglobinuria

and subsequent acute kidney injury.

Stings of most other species cause immediate sharp local pain

followed by edema, ecchymosis, and a burning sensation. Symptoms

typically resolve within a few hours, and skin does not slough. Allergic

reactions to the venom sometimes develop.

TREATMENT

Scorpion Stings

Identification of the offending scorpion helps to determine the

course of treatment. Stings of nonlethal species require at most

ice packs, analgesics, or antihistamines. Because most victims

experience only local discomfort, they can be managed at home

with instructions to return to the emergency department if signs

of cranial-nerve or neuromuscular dysfunction develop. Aggressive

supportive care and judicious use of antivenom can reduce or eliminate deaths from more severe envenomations. Keeping the patient

calm and applying pressure dressings and cold packs to the sting

site are measures that decrease the absorption of venom. A continuous IV infusion of midazolam controls the agitation, flailing, and

involuntary muscle movements produced by scorpion stings. Close

monitoring during treatment with this drug and other sedatives or

narcotics is necessary for persons with neuromuscular symptoms

because of the risk of respiratory arrest. Hypertension and pulmonary edema respond to nifedipine, nitroprusside, hydralazine,

or prazosin. Dangerous bradydysrhythmia can be controlled with

atropine.

Commercially prepared antivenins are available in several countries for some of the most dangerous scorpion species. An FDAapproved C. sculpturatus IgG F(ab’)2

 antivenin in horse serum is

available. IV administration of antivenin rapidly reverses cranial-nerve

dysfunction and muscular symptoms.

■ HYMENOPTERA STINGS

Bees, wasps, hornets, yellow jackets, and ants (all of the insect order

Hymenoptera) sting in defense or to subdue their prey. Their venoms

contain a wide array of amines, peptides, and enzymes that cause local

and systemic reactions. Although the toxic effect of multiple stings can

be fatal to a human, nearly all of the ≥100 deaths due to hymenopteran

stings in the United States each year result from type 1, immediate-type

allergic reactions.

Bee and Wasp Stings The stinger of the honeybee (Apis mellifera)

is unique in being barbed. The stinging apparatus and attached

venom sac tear loose from the honeybee’s body, and muscular contractions of the venom sac continue to infuse venom into the skin. Other

kinds of bees, ants, and wasps have smooth stinging mechanisms and

can sting numerous times in succession. Generally, a person sustains

just one sting from a bee or social wasp unless a nest was disturbed.

Africanized honeybees (now present in South and Central America

and the southern and western United States) respond to minimal

intrusions more aggressively. The sting of an Africanized bee contains

less venom than that of its non-Africanized relatives, but victims tend

to sustain far more stings and thus receive a far greater overall volume

of venom. Most patients who report having sustained a “bee sting” are

more likely to have encountered stinging wasps instead.

The venoms of different kinds of hymenopterans are biochemically and immunologically distinct. Direct toxic effects are mediated

by mixtures of low-molecular-weight compounds such as serotonin,

histamine, acetylcholine, and several kinins. Polypeptide toxins in

honeybee venom include mellitin, which damages cell membranes;

mast cell–degranulating protein, which causes histamine release; the

neurotoxin apamin; and the anti-inflammatory compound adolapin.

Enzymes in venom include hyaluronidase and phospholipases. There

appears to be little cross-sensitization between the venoms of honeybees and wasps.

Uncomplicated hymenopteran stings cause immediate pain, a

wheal-and-flare reaction, and local edema, all of which usually subside

in a few hours. Multiple stings can lead to vomiting, diarrhea, generalized edema, dyspnea, hypotension, and non-anaphylactic circulatory

collapse. Rhabdomyolysis and intravascular hemolysis may cause

renal failure. Death from the direct (nonallergic) effects of venom has

followed stings of several hundred honeybees. Stings to the tongue or

mouth may induce life-threatening edema of the upper airways.

3614 PART 14 Poisoning, Drug Overdose, and Envenomation

Large local reactions accompanied by erythema, edema, warmth,

and tenderness that spread ≥10 cm around the sting site over 1–2 days

are not uncommon. These reactions may resemble bacterial cellulitis

but are caused by hypersensitivity rather than by secondary infection. Such reactions tend to recur on subsequent exposure but are

seldom accompanied by anaphylaxis and are not prevented by venom

immunotherapy.

An estimated 0.4–4.0% of the U.S. population exhibits clinical

immediate-type hypersensitivity to hymenopteran stings, and 15% may

have asymptomatic sensitization manifested by positive skin tests. Persons who experience severe allergic reactions are likely to have similar

or more severe reactions after subsequent stings by the same or closely

related species. Mild anaphylactic reactions to insect stings, as to other

causes, consist of nausea, abdominal cramping, generalized urticaria or

angioedema, and flushing. Serious reactions, including upper airway

edema, bronchospasm, hypotension, and shock, may be rapidly fatal.

Severe reactions usually begin within 10 min of the sting and only

rarely develop after 5 h.

TREATMENT

Bee and Wasp Stings

Honeybee stingers embedded in the skin should be removed as

soon as possible to limit the quantity of venom delivered. The

stinger and venom sac may be scraped off with a blade, a fingernail,

or the edge of a credit card or may be removed with forceps. The site

should be cleansed and disinfected and ice packs applied to slow the

spread of venom. Elevation of the affected site and administration

of oral analgesics, oral antihistamines, and topical calamine lotion

help relieve symptoms.

Anaphylactic reactions to bee or wasp venom can be a

life-threatening emergency that requires prompt life-saving actions.

If the individual carries a bee-sting kit, then a subcutaneous injection of epinephrine hydrochloride (0.3 mL of a 1:1000 dilution)

should be considered, with treatment repeated every 20–30 min as

necessary. A tourniquet may slow the spread of venom. The patient

should be transferred to a hospital emergency room where treatment for profound shock, if required, can be administered safely.

Such treatment may entail the use of IV epinephrine and other

vasopressors, intubation or provision of supplemental oxygen, fluid

resuscitation, use of bronchodilators, and parenteral administration

of antihistamines. Patients should be observed for 24 h for recurrent

anaphylaxis, renal failure, or coagulopathy.

Persons with a history of allergy to insect stings should carry an

anaphylaxis kit with a preloaded syringe containing epinephrine for

self-administration. These patients should seek medical attention

immediately after using the kit.

Prophylactic immunotherapy may greatly reduce the risk of

life-threatening reactions to bee and wasp stings. Repeated injections of purified venom produce a blocking IgG antibody response

to venom and reduce the incidence of recurrent anaphylaxis. Honeybee, wasp, and yellow jacket venoms are commercially available

for desensitization and for skin testing. Results of skin tests and

venom-specific radioallergosorbent tests (RASTs) aid in the selection of patients for immunotherapy and guide the design of such

treatment.

■ STINGING ANTS

Stinging ants are an important medical problem in the United States.

Imported fire ants (Solenopsis species) infest southern states from Texas

to North Carolina, with colonies now established in California, New

Mexico, Arizona, and Virginia. Slight disturbances of their mound

nests have provoked massive outpourings of ants and as many as 10,000

stings on a single person. Elderly and immobile persons are at high risk

for attacks when fire ants invade dwellings.

Fire ants attach to skin with powerful mandibles and rotate their

bodies while repeatedly injecting venom with posteriorly situated

stingers. The alkaloid venom consists of cytotoxic and hemolytic

piperidines and several proteins with enzymatic activity. The initial

wheal-and-flare reaction, burning, and itching resolve in ~30 min,

and a sterile pustule develops within 24 h. The pustule ulcerates over

the next 48 h and then heals in ≥1 week. Large areas of erythema and

edema lasting several days are not uncommon and, in extreme cases,

may compress nerves and blood vessels. Anaphylaxis occurs in <2%

of victims; seizures and mononeuritis have been reported. Stings are

treated with ice packs, topical glucocorticoids, and oral antihistamines.

Pustules should be cleansed and then covered with bandages and antibiotic ointment to prevent bacterial infection. Epinephrine administration and supportive measures are indicated for anaphylactic reactions.

Fire ant whole-body extracts are available for skin testing and immunotherapy, which appear to lower the rate of anaphylactic reactions.

European fire (red) ants (Myrmica rubra) have recently become public health pests in the northeastern United States and southern Canada.

The western United States is home to harvester ants (Pogonomyrmex

species). The painful local reaction that follows harvester ant stings

often extends to lymph nodes and may be accompanied by anaphylaxis. The bullet or conga ant (Paraponera clavata) of South America

is known locally as hormiga veinticuatro (“24-hour ant”), a designation

that refers to the 24 h of throbbing, excruciating pain following a sting

that delivers the potent paralyzing neurotoxin poneratoxin.

■ DIPTERAN (FLY AND MOSQUITO) BITES

In the process of feeding on vertebrate blood and tissue fluids, adults of

certain fly species inflict painful bites, inject saliva that may cause vasodilation and produce local allergic reactions, and may transmit diverse

pathogenic agents. Bites of mosquitoes (culicids), tiny “no-see-um”

midges (ceratopogonids), and sand flies (phlebotomines) typically

produce a wheal and a pruritic papule. Small humpbacked black flies

(simuliids) lacerate skin, resulting in a lesion with serosanguineous

discharge that is often painful and pruritic. Regional lymphadenopathy, fever, or anaphylaxis occasionally ensues. The widely distributed

deerflies and horseflies as well as the tsetse flies of Africa are stout

flies that attack during the day and produce large and painful bleeding

punctures. House flies (Musca domestica) do not consume blood but

use rasping mouthparts to scarify skin and feed upon tissue fluids and

salt. Beyond direct injury from bites of any kind of fly, risks include

transmission of diverse pathogens and secondary bacterial infection

of the lesion.

TREATMENT

Fly and Mosquito Bites

Treatment of fly bites is symptom based. Topical application of

antipruritic agents, glucocorticoids, or antiseptic lotions may relieve

itching and pain. Allergic reactions may require oral antihistamines. Antibiotics may be necessary for the treatment of large bite

wounds that become secondarily infected.

■ FLEA BITES

Common human-biting fleas include the dog and cat fleas (Ctenocephalides species) and the rat flea (Xenopsylla cheopis), which infest

their respective hosts and their nests and resting sites. Sensitized

persons develop erythematous pruritic papules (papular urticaria) and

occasionally vesicles and bacterial superinfection at the site of the bite.

Symptom-based treatment consists of antihistamines, topical glucocorticoids, and topical antipruritic agents.

Flea infestations are eliminated by removal and treatment of animal

nests, frequent cleaning of pet bedding, and application of contact

and systemic insecticides to pets and the dwelling. Flea infestations

in the home may be abated or prevented if pets are regularly treated

with veterinary antiparasitic agents, insect growth regulators, or chitin

inhibitors.

Tunga penetrans, like other fleas, is a wingless, laterally flattened

insect that feeds on blood. Also known as the chigoe flea, sand flea,

3615Ectoparasite Infestations and Arthropod Injuries CHAPTER 461

or jigger (not to be confused with the chigger), it occurs in tropical

regions of Africa and the Americas. Adult female chigoes live in sandy

soil and burrow under the skin, usually between toes, under nails, or

on the soles of bare feet. Gravid chigoes engorge on the host’s blood

and grow from pinpoint to pea size during a 2-week interval. They

produce lesions that resemble a white pustule with a central black

depression and that may be pruritic or painful. Occasional complications include tetanus, bacterial infections, and autoamputation of

toes (ainhum). Tungiasis is treated by removal of the intact flea with

a sterile needle or scalpel, tetanus vaccination, and topical application

of antibiotics.

■ HEMIPTERAN/HETEROPTERAN (TRUE BUG)

BITES

Most true bugs feed on plants, but some are predaceous or feed on

blood. In order to feed or to defend themselves, they may inflict bites

that produce allergic reactions and are sometimes painful. Bites of the

cone-nose or “kissing bugs” (family Reduviidae) tend to occur at night

and are painless. Reactions to such bites depend on prior sensitization

and include tender and pruritic papules, vesicular or bullous lesions,

extensive urticaria, fever, lymphadenopathy, and (rarely) anaphylaxis.

Bug bites are treated with topical antipruritic agents or oral antihistamines. Persons with anaphylactic reactions to reduviid bites should

keep an epinephrine kit available. Some reduviids transmit Trypanosoma cruzi, the agent of New World trypanosomiasis (Chagas disease)

(Chap. 227).

The cosmopolitan and tropical bed bugs (Cimex lectularius and

C.  hemipterus) hide in crevices of mattresses, bed frames and other

furniture, walls, and picture frames and under loose wallpaper, actively

seeking blood meals at night. These bugs are now a common pest in

homes, dormitories, and hotels; on cruise ships; and even in medical

facilities. Their bite is painless. Bites on persons without prior exposure

to bedbugs may not be noticeable. Persons sensitized to bed bug saliva

develop erythema, itching, and wheals around a central hemorrhagic

punctum. Reactions may manifest within minutes of the bites, or they

may be delayed for days or even a week or more. Bed bugs are not

known to transmit pathogens.

■ CENTIPEDE BITES AND MILLIPEDE DERMATITIS

Two groups of myriapods (“many-footed” arthropods) can harm

humans. Centipedes, with one pair of legs per body segment, are

fast-moving, aggressive, and carnivorous. They stun and kill their

prey—usually other arthropods, earthworms, and rarely small

vertebrates—with a venomous bite. The fangs of centipedes of the

genus Scolopendra can penetrate human skin and deliver a venom

that produces intense burning pain, swelling, erythema, and sterile

lymphangitis. Dizziness, nausea, and anxiety are described occasionally, and rhabdomyolysis and renal failure have been reported. Treatment includes washing of the site, application of cold dressings, oral

analgesic administration or local lidocaine infiltration, and tetanus

prophylaxis.

Millipedes, with two pairs of legs per segment, are slow-moving,

docile, and feed mostly on decaying plant materials. They do not bite,

but some secrete defensive fluids that may burn and discolor human

skin. Affected skin turns brown overnight and may blister and exfoliate. Secretions in the eye cause intense pain and inflammation that

can result in corneal ulcers and even blindness. Management includes

irrigation with copious amounts of water or saline, use of analgesics,

and local care of denuded skin.

■ CATERPILLAR STINGS AND DERMATITIS

Caterpillars of several moth species are covered with hairs or spines

that produce mechanical irritation and may contain or be coated with

venom. Contact with these caterpillars or their hairs may lead to erucism (a pruritic urticarial or papular rash) or caterpillar envenomation.

The response typically consists of an immediate burning sensation

followed by local swelling and erythema and occasionally by regional

lymphadenopathy, nausea, vomiting, and headache. A rare reaction to

a South American caterpillar, Lonomia obliqua, can cause disseminated

coagulopathy and fatal hemorrhagic shock.

Dermatitis is most often associated with caterpillars of io, puss,

saddleback, and browntail moths in North America and with the oak

processionary moth in Europe. Even contact with detached hairs of

other caterpillars, such as gypsy moth larvae, can later produce erucism. Spines may be deposited on tree trunks or drying laundry or may

be airborne and cause irritation of the eyes and upper airways. Treatment of caterpillar stings consists of repeated application of adhesive

or cellophane tape to remove the hairs, which can then be identified

microscopically. Local ice packs, topical glucocorticoids, and oral antihistamines relieve symptoms.

Few adult moths cause human health problems. Adult yellowtail

moths (Hylesia species), found mainly in coastal mangrove zones along

the eastern coast of Central and South America, have bodies that are

covered by fine hairs or setae. The hairs on the ventral surface can

detach and, when in contact with human skin, cause an extremely pruritic reaction called “Carapito itch.” This issue is especially problematic

when the moths have population booms, creating swarms around

coastal communities.

■ BEETLE VESICATION AND DERMATITIS

Several families of beetles have independently developed the ability to

produce chemically unrelated vesicating toxins. When disturbed, blister beetles (family Meloidae) exude cantharidin, a low-molecular-weight

toxin that produces thin-walled blisters (≤5 cm in diameter) 2–5 h after

contact. The blisters are not painful or pruritic unless broken. They

resolve without treatment in ≤10 days. Nephritis may follow unusually

heavy cantharidin exposure.

The hemolymph of certain rove beetles (Paederus species, Staphylinidae family) contains pederin, a potent vesicant. When these beetles are

crushed or brushed against the skin, the released fluid causes painful,

red, flaccid bullae. These beetles occur worldwide but are most numerous and problematic in parts of Africa (where they are called “Nairobi

fly”) and southwestern Asia. Ocular lesions may develop after impact

with flying beetles at night or unintentional transfer of the vesicant on

the fingers. Treatment is rarely necessary, although ruptured blisters

should be kept clean and bandaged.

Larvae of common carpet beetles are adorned with dense arrays

of ornate hairs called hastisetae. Contact with these larvae or their

setae results in delayed dermal reactions in sensitized individuals. The

lesions are commonly mistaken for bites of bed bugs.

■ DELUSIONAL INFESTATIONS

The groundless conviction that one is infested with arthropods or

other parasites (Ekbom syndrome, delusory parasitosis, delusions of

parasitosis, and perhaps Morgellons syndrome) is extremely difficult

to treat and, unfortunately, is not uncommon (Fig. 461-2). Patients

describe uncomfortable sensations of something moving in or on their

skin. Excoriations and self-induced ulcerations typically accompany

the pruritus, dysesthesias, and imaginary insect bites. Patients often

believe that some invisible or as yet undescribed creatures are infesting

their skin, clothing, homes, or environment in general. Frequently,

patients submit as evidence of infestation specimens that consist of

plant-feeding and nonbiting peridomestic arthropods, pieces of skin,

vegetable matter, lint, and other inanimate detritus. In the evaluation of

a patient with possible delusional parasitosis, it is imperative to rule out

true infestations and bites by arthropods, endocrinopathies, sensory

disorders due to neuropathies, opiate and other drug use, environmental irritants (e.g., fiberglass threads), and other causes of tingling or

prickling sensations. Frequently, such patients repeatedly seek medical

consultations, resist alternative explanations for their symptoms, and

exacerbate their discomfort by self-treatment. Long-term pharmacotherapy with pimozide or other psychotropic agents has been more

helpful than psychotherapy in treating this disorder. Patients with delusory parasitosis often develop the unshakeable conviction that they are

infested by a previously unknown pathogen, while their personal lives,

family support, and employment collapse around them.

3616 PART 14 Poisoning, Drug Overdose, and Envenomation

■ FURTHER READING

Arlia LG, Morgan MS: A review of Sarcoptes scabiei: Past, present

and future. Parasit Vectors 10:297, 2017.

Goddard J: Infectious Diseases and Arthropods, 3rd ed. Totowa, NJ,

Humana Press, 2018.

Hinkle N: Ekbom syndrome: The challenge of “invisible bug” infestations. Annu Rev Entomol 55:77, 2010.

Mathison BA, Pritt BS : Laboratory identification of arthropod ectoparasites. Clin Microbiol Rev 27:48, 2014.

McGraw TA, Turiansky MC: Cutaneous myiasis. J Am Acad Dermatol 58:907, 2008.

Moraru GM, Goddard J II: The Goddard Guide to Arthropods of

Medical Importance, 7th ed. Boca Raton, FL, CRC Press, 2019.

Mullen G, Durden L: Medical and Veterinary Entomology, 2nd ed.

Amsterdam, Academic Press, 2009.

Pollack RJ, Marcus L: A travel medicine guide to arthropods of

medical importance. Infect Dis Clin North Am 19:169, 2005.

Richards SL et al: Do tick attachment times vary between different

tick–pathogen systems? Environments 4:37, 2017.

Ryan NM et al: Treatments for latrodectism—A systematic review on

their clinical effectiveness. Toxins 9:148, 2017.

Saucier JR: Arachnid envenomation. Emerg Med Clin North Am

22:405, 2004.

Steen CJ et al: Insect sting reactions to bees, wasps, and ants. Int J

Dermatol 44:91, 2005.

Thomas C et al: Ectoparasites: Scabies. J Am Acad Dermatol 82:533,

2020.

Vetter RS, Isbister GK: Medical aspects of spider bites. Annu Rev

Entomol 53:409, 2008.

FIGURE 461-2 Real (left) versus delusional (right) infestation: comparable images of the lower backs of two young adults with multiple lesions. Left: A young woman

developed innumerable widespread lesions during a camping ecotour near Manaus, Brazil. Note scattered clusters of irregularly spaced lesions, accompanied by dozens

of single or isolated lesions, consistent with the semi-random feeding pattern of biting flies. Lesions appear to be in roughly the same stage of development, a feature

indicating that they were acquired at roughly the same time. No lesions were present before her ecotour; none have arisen since. This patient scratches the intensely

pruritic lesions and causes superficial erosions. Unexcoriated lesions are also present on her midback, where she cannot scratch. Right: A young man has innumerable

widespread lesions that have accumulated for several years, with a few new lesions appearing several times a week. His lesions are in various stages of development

(fresh, crusted, re-epithelialized, pigmented, and scarred), a feature indicating a long-standing process. The lesions are distributed in a regular pattern consistent with

periodic “excavations” to remove alleged parasites that he believes are crawling through his skin. Scarring is due to manipulations that create dermal ulcers rather than

superficial excoriations and erosions. Parts of his upper midback, where he cannot scratch, are free of lesions.

Disorders Associated with Environmental Exposures PART 15

462

■ EPIDEMIOLOGY

Mountains cover one-fifth of the earth’s surface; 140 million people

live permanently at altitudes ≥2500 m, and 100 million people travel to

high-altitude locations each year. Skiers in the Alps or Aspen; tourists

to La Paz, Ladakh, or Lahsa; religious pilgrims to Kailash-Manasarovar

or Gosainkunda; trekkers and climbers to Kilimanjaro, Aconcagua, or

Everest; miners working in high-altitude sites in South America; and

military personnel deployed to high-altitude locations are all at risk

of developing acute mountain sickness (AMS), high-altitude cerebral

edema (HACE), high-altitude pulmonary edema (HAPE), and other

altitude-related problems. AMS is the benign form of altitude illness,

whereas HACE and HAPE are life-threatening. Altitude illness is likely

to occur above 2500 m but has been documented even at 1500–2500 m.

In the Mount Everest region of Nepal, ~50% of trekkers who walk to

altitudes >4000 m over ≥5 days develop AMS, as do 84% of people who

fly directly to 3860 m. The incidences of HACE and HAPE are much

lower than that of AMS, with estimates in the range of 0.1–4%. Finally,

reentry HAPE, which in the past was generally limited to highlanders

(long-term residents of altitudes >2500 m) in the Americas, is now

being seen in Himalayan and Tibetan highlanders—and often misdiagnosed as a viral illness—as a result of recent rapid air, train, and

motorable-road access to high-altitude settlements.

■ PHYSIOLOGY

Ascent to a high altitude subjects the body to a decrease in barometric

pressure that results in a decreased partial pressure of oxygen in the

inspired gas in the lungs. This change leads in turn to less pressure,

driving oxygen diffusion from the alveoli and throughout the oxygen

cascade. A normal initial “struggle response” to such an ascent includes

increased ventilation—the cornerstone of acclimatization—mediated

by the carotid bodies. Hyperventilation may cause respiratory alkalosis

and dehydration. Respiratory alkalosis may be extreme, with an arterial

blood pH of >7.7 (e.g., at the summit of Everest). Alkalosis may depress

the ventilatory drive during sleep, with consequent periodic breathing

and hypoxemia. During early acclimatization, renal suppression of carbonic anhydrase and excretion of dilute alkaline urine combat alkalosis

and tend to bring the pH of the blood to normal. Other physiologic

changes during normal acclimatization include increased sympathetic

tone; increased erythropoietin levels, leading to increased hemoglobin

levels and red blood cell mass; increased tissue capillary density and

mitochondrial numbers; and higher levels of 2,3-bisphosphoglycerate,

enhancing oxygen utilization. Even with normal acclimatization, however, ascent to a high altitude decreases maximal exercise capacity (by

~1% for every 100 m gained above 1500 m) and increases susceptibility

to cold injury due to peripheral vasoconstriction. If the ascent is made

faster than the body can adapt to the stress of hypobaric hypoxemia,

altitude-related disease states can result.

■ GENETICS

Hypoxia-inducible factor, which acts as a master switch in highaltitude adaptation, controls transcriptional responses to hypoxia

throughout the body and is involved in the release of vascular

endothelial growth factor (VEGF) in the brain, erythropoiesis, and

other pulmonary and cardiac functions at high altitudes. In particular,

the gene EPAS1, which codes for transcriptional regulator hypoxiainducible factor 2α, appears to play an important role in the adaptation

of Tibetans living at high altitude, resulting in lower hemoglobin concentrations than are found in Han Chinese or South American highlanders. Other genes implicated include EGLN1 and PPARA, which are

also associated with hemoglobin concentration. Some evidence indicates that these genetic changes occurred within the past 3000 years,

which is very fast in evolutionary terms. An intriguing question is

whether the Sherpas’ well-known mountain-climbing ability is partially attributable to their Tibetan ancestry, with overrepresentation of

variants of EPAS. A striking recent finding is that some of these genetic

characteristics may stem from those of Denisovan hominids who were

contemporaries of the Neanderthals.

For acute altitude illness, a single gene variant is unlikely to be

found, but differences in the susceptibility of individuals and populations, familial clustering of cases, and a positive association of some

genetic variants all clearly support a role for genetics.

■ ACUTE MOUNTAIN SICKNESS AND HIGHALTITUDE CEREBRAL EDEMA

AMS is a neurologic syndrome characterized by nonspecific symptoms

(headache, nausea, fatigue, and dizziness), with a paucity of physical

findings, developing 6–12 h after ascent to a high altitude. AMS is a

clinical diagnosis. For uniformity in research studies, the Lake Louise

Scoring System, created at the 1991 International Hypoxia Symposium,

is generally used without the sleep disturbance score. AMS must be

distinguished from exhaustion, dehydration, hypothermia, alcoholic

hangover, and hyponatremia. AMS and HACE are thought to represent

opposite ends of a continuum of altitude-related neurologic disorders.

HACE (but not AMS) is an encephalopathy whose hallmarks are

ataxia and altered consciousness with diffuse cerebral involvement

but generally without focal neurologic deficits. Progression to these

signal manifestations can be rapid. Papilledema and, more commonly,

retinal hemorrhages may develop. In fact, retinal hemorrhages occur

frequently at ≥5000 m, even in individuals without clinical symptoms

of AMS or HACE.

Risk Factors The most important risk factors for the development

of altitude illness are the rate of ascent and a prior history of highaltitude illness. Exertion is a risk factor, but lack of physical fitness is

not. An attractive but still speculative hypothesis proposes that AMS

develops in people who have inadequate cerebrospinal capacity to

buffer the brain swelling that occurs at high altitude. Children and

adults seem to be equally affected, but people >50 years of age may be

less likely to develop AMS than younger people. In general, there is no

gender difference in AMS incidence. Sleep desaturation—a common

phenomenon at high altitude—is associated with AMS. Debilitating

fatigue consistent with severe AMS on descent from a summit is an

important risk factor for death in mountaineers. A prospective study

involving trekkers and climbers who ascended to altitudes between

4000 and 8848 m showed that high oxygen desaturation and low ventilatory response to hypoxia during exercise are independent predictors

of severe altitude illness. However, because there may be a large overlap

between groups of susceptible and nonsusceptible individuals, accurate cutoff values are hard to define. Prediction is made more difficult

because the pretest probabilities of HAPE and HACE are low. Neck

irradiation or surgery damaging the carotid bodies, respiratory tract

infections, and dehydration appear to be other potential risk factors

for altitude illness. Unless guided by clinical signs and symptoms, pulse

oximeter readings alone on a trek should not be used to predict AMS.

Pathophysiology Hypobaric hypoxia is the main trigger for altitude illness. In established AMS, raised intracranial pressure, increased

sympathetic activity, relative hypoventilation, fluid retention and

redistribution, and impaired gas exchange have all been well noted;

these factors may play an important role in the pathophysiology of

AMS. Severe hypoxemia can lead to a greater than normal increase in

cerebral blood flow. However, the exact mechanisms underlying AMS

and HACE are unknown. Evidence points to a central nervous system

process. MRI studies have suggested that vasogenic (interstitial) cerebral edema is a component of the pathophysiology of HACE. In the

Altitude Illness

Buddha Basnyat, Geoffrey Tabin

3618 PART 15 Disorders Associated with Environmental Exposures

setting of high-altitude illness, the MRI findings shown in Fig. 462-1

are confirmatory of HACE, with increased signal in the white matter

and particularly in the splenium of the corpus callosum. In addition,

hemosiderin deposits in the corpus callosum have been characterized

as long-lasting footprints of HACE. Quantitative analysis in an MRI

study revealed that hypoxia is associated with mild vasogenic cerebral

edema irrespective of AMS. This finding is in keeping with case reports

of suddenly symptomatic brain tumors and of cranial nerve palsies

without AMS at high altitudes. Vasogenic edema may become cytotoxic (intracellular) in severe HACE.

Impaired cerebral autoregulation in the presence of hypoxic cerebral

vasodilation and altered permeability of the blood-brain barrier due

to hypoxia-induced chemical mediators like histamine, arachidonic

acid, and VEGF may all contribute to brain edema. In 1995, VEGF was

first proposed as a potent promoter of capillary leakage in the brain at

high altitude, and studies in mice have borne out this role. Although

studies of VEGF in climbers have yielded inconsistent results regarding its association with altitude illness, indirect evidence of a role for

this growth factor in AMS and HACE comes from the observation

that dexamethasone, when used in the prevention and treatment of

these conditions, blocks hypoxic upregulation of VEGF. Other factors

in the development of cerebral edema may be the release of calciummediated nitric oxide and neuronally mediated adenosine, which may

promote cerebral vasodilation. Venous outflow obstruction resulting

in increased brain capillary pressure is also thought to play an important role in the development of HACE. Lesions in the globus pallidum

(which is sensitive to hypoxia) leading to Parkinson’s disease have been

reported to be complications of HACE.

The pathophysiology of the most common and prominent symptom

of AMS—headache—remains unclear because the brain itself is an

insensate organ; only the meninges contain trigeminal sensory nerve

fibers. The cause of high-altitude headache is multifactorial. Various

chemicals and mechanical factors activate a final common pathway, the

trigeminovascular system. In the genesis of high-altitude headache, the

response to nonsteroidal anti-inflammatory drugs and glucocorticoids

provides indirect evidence for involvement of the arachidonic acid

pathway and inflammation.

Prevention and Treatment (Table 462-1) Gradual ascent, with

adequate time for acclimatization, is the best method for the prevention

of altitude illness. Even though there may be individual variation in the

rate of acclimatization, a conservative approach would be a graded

ascent of ≤300 m from the previous day’s sleeping altitude above 3000 m,

and taking every third day of gain in sleeping altitude as an extra day

for acclimatization is helpful. Spending one night at an intermediate

altitude before proceeding to a higher altitude may enhance acclimatization and attenuate the risk of AMS. Another protective factor in AMS

is high-altitude exposure during the preceding 2 months; for example,

the incidence and severity of AMS at 4300 m are reduced by 50% with

an ascent after 1 week at an altitude ≥2000 m rather than with an ascent

from sea level. However, regarding the benefits of acclimatization,

clear-cut randomized studies are lacking. Repeated exposure at low

altitudes to hypobaric or normobaric hypoxia is termed preacclimatization. Preacclimatization is gaining popularity. For example, many

Everest climbers in the spring of 2019 claimed to use commercially

available “tents” at home with a hypoxic environment for weeks to

months in preparation for the climb. However, the optimal method

based on robust studies for preacclimatization is yet to be determined.

Clearly, a flexible itinerary that permits additional rest days will

be helpful. Sojourners to high-altitude locations must be aware of the

symptoms of altitude illness and should be encouraged not to ascend

further if these symptoms develop. Any hint of HAPE (see below) or

HACE mandates descent. Proper hydration (but not overhydration) in

high-altitude trekking and climbing, aimed at countering fluid loss due

to hyperventilation and sweating, may play a role in avoiding AMS.

Pharmacologic prophylaxis at the time of travel to high altitudes is

warranted for people with a history of AMS or when a graded ascent

and acclimatization are not possible—e.g., when rapid ascent is necessary for rescue purposes or when flight to a high-altitude location is

required. Acetazolamide is the drug of choice for AMS prevention. It

inhibits renal carbonic anhydrase, causing prompt bicarbonate diuresis

that leads to metabolic acidosis and hyperventilation. Acetazolamide

(125 mg twice daily), administered for 1 day before ascent and continued for about 3 days at the same altitude, is effective. Treatment

can be restarted if symptoms return after discontinuation of the drug.

FIGURE 462-1 T2 magnetic resonance image of the brain of a patient with highaltitude cerebral edema (HACE) shows marked swelling and a hyperintense

posterior body and splenium of the corpus callosum (area with dense opacity). The

patient, a climber, went on to climb Mount Everest about 9 months after this episode

of HACE. (Source: FJ Trayers 3rd: Wilderness preventive medicine. Wilderness

Environ Med 15:53, 2004.)

TABLE 462-1 Management of Altitude Illness

CONDITION MANAGEMENT

Acute mountain sickness

(AMS), milda

Discontinuation of ascent

Treatment with acetazolamide (250 mg q12h)

Descentb

AMS, moderatea Immediate descent for worsening symptoms

Use of low-flow oxygen if available

Treatment with acetazolamide (250 mg q12h) and/or

dexamethasone (4 mg q6h)c

Hyperbaric therapyd

High-altitude cerebral

edema (HACE)

Immediate descent or evacuation

Administration of oxygen (2–4 L/min)

Treatment with dexamethasone (8 mg PO/IM/IV; then

4 mg q6h)

Hyperbaric therapy if descent is not possible

High-altitude pulmonary

edema (HAPE)

Immediate descent or evacuation

Minimization of exertion while patient is kept warm

Administration of oxygen (4–6 L/min) to bring O2

saturation to >90%

Adjunctive therapy with nifedipinee

 (30 mg, extendedrelease, q12h)

Hyperbaric therapy if descent is not possible

a

Categorization of cases as mild or moderate is a subjective judgment based on

the severity of headache and the presence and severity of other manifestations

(nausea, fatigue, dizziness). b

No fixed altitude is specified; the patient should

descend to a point below that at which symptoms developed. c

Acetazolamide treats

and dexamethasone masks symptoms. For prevention (as opposed to treatment) of

AMS, 125 mg of acetazolamide q12h or (when acetazolamide is contraindicated—

e.g., in people with a history of sulfa anaphylaxis) 4 mg of dexamethasone q12h

may be used. d

In hyperbaric therapy (Fig. 462-2), the patient is placed in a portable

altitude chamber or bag to simulate descent. e

Nifedipine at this dose is also

effective for the prevention of HAPE, as are tadalafil (10 mg twice daily), sildenafil

(50 mg three times per day), and dexamethasone (8 mg twice daily). Preventative

therapy should be continued for about 3 days after arriving at the target altitude.

If prompt descent follows arrival at target altitude, continuation of preventative

therapy is unnecessary.