InternalMed_Harrison

InternalMed_Harrison. The human itch mite, Sarcoptes scabiei var. hominis, is a common cause of itching dermatosis, infesting ~300 million persons worldwide at any one time. Gravid female mites (~0.3 mm in length) burrow superficially within the stratum corneum, depositing three or fewer 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 sex with multiple partners. Generally, these mites die within a day or so in the absence of host contact. Transmission via sharing of contaminated bedding or clothing occurs far less frequently than is often thought. In the United States, scabies may account for up to 5% of visits to dermatologists. Outbreaks occur in preschools, hospitals, nursing


InternalMed_Harrison

InternalMed_Harrison. or clothing occurs far less frequently than is often thought. In the United States, scabies may account for up to 5% of visits to dermatologists. Outbreaks occur in preschools, hospitals, nursing homes, and other residential institutions.


InternalMed_Harrison

InternalMed_Harrison. The itching and rash associated with scabies derive from a sensitization reaction to the mites and their secretions/excretions. A person’s initial infestation 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 histiocytes, and a generalized hypersensitivity rash later develops in remote sites. Immunity and associated scratching limit most infestations to <15 mites per person. Hyperinfestation with thousands of mites, a condition known as crusted scabies (formerly termed Norwegian scabies), may result from glucocorticoid use, immunodeficiency, and neurologic or psychiatric illnesses that limit the itch and/or the scratch response.


InternalMed_Harrison

InternalMed_Harrison. 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. Scabetic lesions are most common on the volar wrists and along the digital web spaces. In males, the penis and scrotum become involved. Small papules and vesicles, often accompanied by eczematous plaques, pustules, or nodules, appear symmetrically at those sites; 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


InternalMed_Harrison

InternalMed_Harrison. 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 classic scabies in hospitals.


InternalMed_Harrison

InternalMed_Harrison. 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 household 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 skin biopsies (including 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, the diagnosis is based on a history of pruritus, a clinical examination, and an epidemiologic link. Diverse kinds of dermatitis from other causes frequently are misdiagnosed as scabies, particularly in presumed “outbreak” situations. Scabies mites of other animals may cause transient irritation, but they do not reside


InternalMed_Harrison

InternalMed_Harrison. from other causes frequently are misdiagnosed as scabies, particularly in presumed “outbreak” situations. Scabies mites of other animals may cause transient irritation, but they do not reside or reproduce in human hosts.


InternalMed_Harrison

InternalMed_Harrison. Permethrin cream (5%) is less toxic than 1% lindane preparations and is effective against lindane-tolerant infestations. Scabicides are applied thinly but thoroughly behind the ears and from the neck down after bathing—with careful application to interdigital spaces and the umbilicus and under the fingernails—and are removed 8–14 h later with soap and water. Successful treatment of crusted scabies requires preapplication of a keratolytic agent such as 6% salicylic acid and then of scabicides to the scalp, face, and ears. Repeated treatments or the sequential use of several agents may be necessary. Ivermectin has not been approved by the U.S. Food and Drug Administration (FDA) for treatment of any form of scabies, but a single oral dose (200 μg/kg) is effective in otherwise healthy persons; patients with crusted scabies may require two doses separated by an interval of 1–2 weeks. All FDA-approved scabicides are available solely by prescription.


InternalMed_Harrison

InternalMed_Harrison. Within 1 day of effective treatment, scabies infestations become noncommunicable, but the pruritic hypersensitivity dermatitis induced by the now-dead mites and their remnant products frequently persists for weeks. Unnecessary re-treatment with topical agents may provoke contact dermatitis. Antihistamines, salicylates, and calamine lotion relieve itching during treatment, and topical glucocorticoids are useful for pruritus that lingers after effective treatment. To prevent reinfestations, bedding and clothing should be washed and dried on high heat or heat-pressed. Close contacts of confirmed cases, even if asymptomatic, should be treated simultaneously.


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InternalMed_Harrison. Chiggers are the larvae of trombiculid (harvest) mites that normally feed on mice 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 mammalian 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 stylostomal saliva is highly antigenic and causes exceptionally pruritic papular, papulovesicular, or papulourticarial lesions (≤2 cm in diameter). In people previously sensitized to salivary antigens, the papules develop within hours of attachment. While attached, mites appear as tiny red vesicles on the skin. Generally, lesions vesicate and develop a hemorrhagic base. Scratching, however, invariably destroys the body of a mite. Itching and burning often persist for weeks. The rash is common on the ankles and areas where clothing


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InternalMed_Harrison. and develop a hemorrhagic base. Scratching, however, invariably destroys the body of a mite. Itching and burning often persist for weeks. The rash is common on the ankles and areas where clothing obstructs the further wanderings of the mites. Repellents are useful for preventing chigger bites.


InternalMed_Harrison

InternalMed_Harrison. Many kinds of mites that are 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, various songbirds, and small mammals and are abundant in and around their hosts’ nests. After their natural hosts die or leave the nest, these mites frequently invade human habitations. Although the mites are rarely seen because of their small size, their bites can be painful and pruritic. Once confirmed as the cause of irritation, rodentand bird-associated mites are best eliminated by excluding their hosts, removing the nests, and cleaning and treating the nesting area with appropriate acaricides. Pyemotes and other mites that infest grain, straw, cheese, hay, or other products occasionally produce similar episodes of rash and discomfort and may produce a unique dermatologic “comet sign” lesion—a paisley-shaped urticarial


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InternalMed_Harrison. infest grain, straw, cheese, hay, 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.


InternalMed_Harrison

InternalMed_Harrison. 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. Oral antihistamines or topical steroids may suppress mite-induced pruritus temporarily but do not eliminate the mites.


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InternalMed_Harrison. Ticks attach superficially to skin and feed painlessly; blood is their only food. Their salivary secretions are biologically active 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) and soft (argasid) ticks. Generally, soft ticks attach for <1 h, leaving red macules after they drop off. Some species in Africa, the western United States, and Mexico produce painful hemorrhagic lesions. Hard ticks are much more common and transmit most of the 2745 tick-borne infections that are familiar to physicians and patients. Hard ticks attach to the host and feed for several days or sometimes for >1 week. 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, occasionally develops. Chronic nodules (persistent tick-bite granulomas) can be several centimeters in diameter


InternalMed_Harrison

InternalMed_Harrison. and may be surrounded by an erythematous rim. A necrotic eschar, called a tâche noire, 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 surgical excision. Tick-induced fever, unas sociated with transmission of any pathogen, is often accompanied by headache, nausea, and malaise but usually resolves ≤36 h after the tick is removed.


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InternalMed_Harrison. 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 more than 60 kinds of ticks, although in the United States dog and wood ticks (Dermacentor species) are most commonly involved.


InternalMed_Harrison

InternalMed_Harrison. 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. Removal of the tick generally leads to rapid 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. Diagnosis depends on finding the tick, which is often hidden beneath scalp hair. An antiserum to the saliva of Ixodes holocyclus, the usual cause of tick paralysis in Australia, effectively reverses paralysis caused by these ticks.


InternalMed_Harrison

InternalMed_Harrison. Removal of hard ticks during the first 36 h of attachment nearly always prevents transmission of the agents of Lyme disease, babesiosis, anaplasmosis, and ehrlichiosis, although several 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. 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 other substances (in an attempt to induce the tick to detach) merely delay 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 excision. Although somewhat controversial, 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


InternalMed_Harrison

InternalMed_Harrison. 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, administering prophylaxis with a single oral dose of doxycycline (200 mg) within 72 h of tick removal is appropriate in adult patients with bites thought to be associated with deer ticks (Fig. 475-1) in Lyme disease–endemic areas from Maryland to Maine and in Wisconsin and Minnesota.


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InternalMed_Harrison. Nymphs and adults of all three kinds of human lice feed at least once a day, ingesting human blood exclusively. Head lice (Pediculus capitis) infest mainly the hair of the scalp, body lice (Pediculus humanus) the clothing, and crab or pubic lice (Pthirus pubis) 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 hatches. Empty eggs may remain affixed for months thereafter.


InternalMed_Harrison

InternalMed_Harrison. In North America, head lice infest ~1% of elementary school-age children. Head lice are transmitted mainly by direct head-to-head contact rather than by fomites such as shared headgear, bed linens, hairbrushes, and other grooming implements. Chronic infestations by head lice tend to be asymptomatic. Pruritus, due mainly to hypersensitivity to the louse’s saliva, generally is transient and mild. Head lice FIGUrE 475-1 Deer ticks (Ixodes scapularis, black-legged ticks) on a U.S. penny: larva(below ear),nymph(right),adultmale(above),andadultfemale(left). removed from a person succumb to desiccation and starvation within ~1 day. Head lice are not known to serve as a natural vector for any pathogens.


InternalMed_Harrison

InternalMed_Harrison. Body lice remain on clothing except when feeding and generally succumb in ≤2 days if separated from their host. In most Western countries, body lice are generally found on a small proportion of indigent persons but may become increasingly prevalent after upheaval associated with natural or human-caused disasters, when homeless victims are in close contact with infested individuals with whom they share accommodations. Body lice are acquired by direct contact or by sharing of infested clothing and bedding. These lice are vectors for the agents of louse-borne (epidemic) typhus (Chap. 211), louse-borne relapsing fever (Chap. 209), and trench fever (Chap. 197). Pruritic lesions from their bites are particularly common around the neckline. Chronic infestations result in a postinflammatory hyperpigmentation and thickening of skin known as vagabond’s disease.


InternalMed_Harrison

InternalMed_Harrison. 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 nits firmly cemented to hairs or in clothing. Many bona fide nits, however, are dead or hatched relics of prior infestation, and pseudo-nits are frequently misconstrued to be signs of a louse infestation. Confirmation of a louse infestation, therefore, best relies on the discovery of a live louse.


InternalMed_Harrison

InternalMed_Harrison. Generally, treatment is warranted only if live lice are discovered. The presence of nits alone is evidence of a former—not necessarily current—infestation. Mechanical removal of lice and their eggs with a fine-toothed louse or nit comb (Fig. 475-2) often fails to eliminate infestations. Treatment of newly identified active infestations generally 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 has been reported. 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


InternalMed_Harrison

InternalMed_Harrison. been reported. 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 a nit (louse-egg) comb.


InternalMed_Harrison

InternalMed_Harrison. from school, this practice increasingly is seen as unjustified and ineffective. 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. 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 refers to infestations by several kinds of fly larvae (maggots) that invade living or necrotic tissues or body cavities and produce different clinical syndromes, depending on the species of fly.


InternalMed_Harrison

InternalMed_Harrison. In forested parts of Central and South America, larvae of the human botfly (Dermatobia hominis) produce furuncular (boil-like) papules or 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 bovine host several days later, the warmth and moisture of the host’s skin stimulate the eggs to hatch. The emerging larvae 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.


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InternalMed_Harrison. The African tumbu fly (Cordylobia anthropophaga) deposits its eggs on damp sand or leaf litter or on drying laundry, particularly that 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 days later. Furuncular myiasis is suggested by uncomfortable lesions with a central breathing pore that emits 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 into the surrounding tissue, but surgical excision is sometimes necessary because upward-pointing spines of some species hold the larvae firmly in place.


InternalMed_Harrison

InternalMed_Harrison. Other fly larvae cause nonfuruncular myiasis. For example, larvae of the horse botfly (Gasterophilus intestinalis) emerge from eggs deposited on the horse’s flanks and may come into contact with and infest human beings. 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. 256). Larvae of rabbit and rodent botflies (Cuterebra species) occasionally cause dermal or tracheopulmonary myiasis.


InternalMed_Harrison

InternalMed_Harrison. 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/Phaenicia species) usually remain superficial and confined to necrotic tissue. Specially raised, sterile “surgical maggots” are sometimes used intentionally for wound debridement. Larvae of screwworm flies, Cochliomyia, and the flesh fly 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.


InternalMed_Harrison

InternalMed_Harrison. The maggots 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.


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InternalMed_Harrison. Pentastomids (tongue worms) 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. Larvae migrate to the nasopharynx and produce an acute self-limiting syndrome—known as halzoun or marrara—characterized by 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. Individuals become infected with another type of tongue worm, Armillifer armillatus, by consuming its eggs in contaminated food or drink or after handling the definitive host, the African python. Larvae encyst in various organs but rarely cause symptoms.


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InternalMed_Harrison. worm, Armillifer armillatus, by consuming its eggs in contaminated food or drink or after handling the definitive host, the African python. Larvae encyst in various organs but rarely cause symptoms. Cysts may require surgical removal as they enlarge during 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.


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InternalMed_Harrison. Medically important leeches are annelid worms that attach to their hosts with chitinous cutting jaws and draw blood through muscular suckers. The medicinal leech (Hirudo medicinalis) is 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.


InternalMed_Harrison

InternalMed_Harrison. Ubiquitous aquatic leeches that parasitize fish, frogs, and turtles readily attach to the skin of human beings and avidly suck blood. More notorious are arboreal land leeches that live among moist vegetation of tropical rain forests. 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 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. 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


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InternalMed_Harrison. 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.


InternalMed_Harrison

InternalMed_Harrison. Internally attached leeches may detach on exposure to gargled saline 2747 or may be removed by forceps.


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InternalMed_Harrison. Of the more than 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 skin and systemic toxicity. Whereas the bites of most spiders are 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 and because injuries attributed to spiders are frequently due to other causes. Except in cases where the patient actually observes a spider immediately associated with the bite or fleeing from the site, lesions reported as spider-bite reactions are most often due to other injuries or to infections with bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).


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InternalMed_Harrison. recluse Spider Bites and Necrotic arachnidism Brown recluse spiders live mainly in the south-central United States and have close relatives in Central and South America, Africa, and the Middle East. Bites by brown recluse spiders usually cause only minor injuries, with edema and erythema. Envenomation, however, occasionally causes severe necrosis of skin and subcutaneous tissue and more rarely causes systemic hemolysis. These spiders are not aggressive toward humans and will bite only if threatened or pressed against the skin. They hide under rocks and logs or in caves and animal burrows. They invade homes and seek dark and undisturbed hiding spots in closets, in folds of clothing, or under furniture and rubbish in storage rooms, garages, and attics. Despite their impressive abundance in some homes, these spiders rarely bite humans. Bites tend to occur while the victim is dressing and are sustained primarily on the hands, arms, neck, and lower abdomen.


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InternalMed_Harrison. Initially, the bite is painless or may produce a stinging sensation. Within the next 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 ≤6 months but may take as long as 3 years if adipose tissue is involved. Local complications include injury to nerves and secondary bacterial infection. Fever, chills, weakness, headache, nausea, vomiting, myalgia, arthralgia, maculopapular rash, 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.


InternalMed_Harrison

InternalMed_Harrison. Initial management includes RICE (rest, ice, compression, elevation). 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 is unnecessary. 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.


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InternalMed_Harrison. 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 2748 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


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InternalMed_Harrison. 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 neurologic 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.


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InternalMed_Harrison. 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 antivenoms for black widow and redback spiders are controversial because of concerns about potential anaphylaxis or serum sickness.


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InternalMed_Harrison. tarantulas and Other Spiders Tarantulas are hairy spiders of which 30 species are found in the United States, mainly in the Southwest. The tarantulas that have become popular household pets are usually imported from Central or South America. Tarantulas bite only when threatened and usually cause no more harm than a 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


InternalMed_Harrison

InternalMed_Harrison. 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.


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InternalMed_Harrison. 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 antivenoms 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.


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InternalMed_Harrison. Scorpions are arachnids that feed on ground-dwelling arthropods and small lizards. 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 more than 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.


InternalMed_Harrison

InternalMed_Harrison. Of the 40 or so scorpion species in the United States, only bark scorpions—e.g., 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


InternalMed_Harrison

InternalMed_Harrison. 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.


InternalMed_Harrison

InternalMed_Harrison. 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. Tissue necrosis and hemolysis may follow stings of the Iranian Hemiscorpius lepturus. 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.


InternalMed_Harrison

InternalMed_Harrison. 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


InternalMed_Harrison

InternalMed_Harrison. 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 bradyarrhythmias can be controlled with atropine.


InternalMed_Harrison

InternalMed_Harrison. Commercially prepared antivenoms are available in several countries for some of the most dangerous species. An FDA-approved C. sculpturatus antivenom in horse serum is now available. IV administration of antivenom rapidly reverses cranial-nerve dysfunction and muscular symptoms. Although effective, cost analyses suggest that antivenoms should be reserved for only the most severe envenomations. Insects that sting in defense or to subdue their prey belong to the order Hymenoptera, which includes bees, wasps, hornets, yellow jackets, and ants. 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 allergic reactions.


InternalMed_Harrison

InternalMed_Harrison. Bee and Wasp Stings The stinger of the honeybee (Apis mellifera) is unique in being barbed. When a bee stings a foe, its stinging apparatus and attached venom sac tear loose from its body. Muscular contraction of the venom sac continues to inject venom into the skin. Other kinds of bees, ants, and wasps have smooth stinging mechanisms and can sting numerous times in succession. Honeybees, bumblebees, and social wasps generally attack only when a colony is disturbed. Africanized honeybees (now present in South and Central America and the southern and western United States) respond to minimal intrusions more aggressively. Whereas the sting of an Africanized bee contains less venom than that of its non-Africanized relatives, victims tend to sustain far more stings and therefore to receive a far greater overall volume of venom. Most patients who report having sustained a “bee sting,” however, are more likely to have encountered stinging wasps instead.


InternalMed_Harrison

InternalMed_Harrison. The venoms of different species 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 that damages cell membranes, mast cell– degranulating protein that 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.


InternalMed_Harrison

InternalMed_Harrison. 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. 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.


InternalMed_Harrison

InternalMed_Harrison. 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 reactions after subsequent stings by the same or closely related species. Occasionally, persons who have had mild reactions earlier in life will experience more serious reactions to subsequent stings. Mild anaphylactic reactions from insect stings, as from other causes, consist of nausea, abdominal cramping, generalized urticaria, flushing, and angioedema. 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.


InternalMed_Harrison

InternalMed_Harrison. 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, the edge of a credit card, or a fingernail 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 analgesics, oral antihistamines, and topical calamine lotion help relieve symptoms. Large local reactions may require a short course of oral therapy with glucocorticoids. Patients with numerous stings should be monitored for 24 h for evidence of renal failure or coagulopathy.


InternalMed_Harrison

InternalMed_Harrison. Anaphylaxis is treated with SC injection of 0.3–0.5 mL of epinephrine hydrochloride in a 1:1000 dilution; treatment is repeated every 20–30 min as necessary. IV epinephrine (2–5 mL of a 1:10,000 solution administered by slow push) is indicated for profound shock. 2749 A tourniquet may slow the spread of venom. Parenteral antihistamines, fluid resuscitation, bronchodilators, supplemental oxygen, intubation, and vasopressors may be required. Patients should be observed for 24 h for recurrent anaphylaxis. 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.


InternalMed_Harrison

InternalMed_Harrison. 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 fire 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.


InternalMed_Harrison

InternalMed_Harrison. 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 fewer than 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


InternalMed_Harrison

InternalMed_Harrison. 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 appears to lower the rate of anaphylactic reactions.


InternalMed_Harrison

InternalMed_Harrison. 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.


InternalMed_Harrison

InternalMed_Harrison. In the process of feeding on vertebrate blood and tissue fluids, adults of certain flies inflict painful bites, produce local allergic reactions, and may transmit pathogenic agents. Bites of mosquitoes, tiny “no-seeum” (ceratopogonid) midges, and phlebotomine sand flies 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 measuring ≤25 mm in length that attack during the day and produce large and painful bleeding punctures. Houseflies (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 2750 of fly, risks include transmission of diverse pathogens and secondary infection


InternalMed_Harrison

InternalMed_Harrison. mouthparts to scarify skin and feed upon tissue fluids and salt. Beyond direct injury from bites of any kind 2750 of fly, risks include transmission of diverse pathogens and secondary infection of the lesion.


InternalMed_Harrison

InternalMed_Harrison. 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. Common human-biting fleas include the dog and cat fleas (Ctenocephalides species) and the rat flea (Xenopsylla cheopis), which infest their respective hosts and the hosts’ 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.


InternalMed_Harrison

InternalMed_Harrison. 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 and insect growth regulators.


InternalMed_Harrison

InternalMed_Harrison. Tunga penetrans, like other fleas, is a wingless, laterally flattened insect that feeds on blood. Also known as the chigoe flea, sand flea, 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.


InternalMed_Harrison

InternalMed_Harrison. Several true bugs of the family Reduviidae inflict bites that produce allergic reactions and are sometimes painful. The cone-nose bugs, so called because of their elongated heads, include the assassin and wheel bugs, which feed on other insects and bite vertebrates only in self-defense, and the kissing bugs, which routinely feed on vertebrate blood. The bites of the night-feeding kissing bugs 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 antipruritics 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 (also called Chagas disease) (Chap. 252).


InternalMed_Harrison

InternalMed_Harrison. The cosmopolitan bedbugs (Cimex species) hide in crevices of mattresses, bed frames and other furniture, walls, and picture frames and under loose wallpaper. Bedbug populations have resurged, recently attaining levels and spreading to an extent not encountered since the mid-twentieth century. These bugs are now a common pest in homes, dormitories, and hotels; on cruise ships; and even in medical facilities. Generally, the bugs hide during the day and take blood meals at night. Their bite is painless, but minutes to days later, sensitized persons develop erythema, itching, and wheals around a central hemorrhagic punctum. Bedbugs are not known to transmit pathogens.


InternalMed_Harrison

InternalMed_Harrison. 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 are docile and 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.


InternalMed_Harrison

InternalMed_Harrison. 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 lepidopterism 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. In the United States, dermatitis is most often associated with caterpillars of the io, puss, saddleback, and brown-tail moths. Even contact with detached hairs of other caterpillars, such as gypsy moth larvae, can later produce a pruritic urticarial or papular rash called 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


InternalMed_Harrison

InternalMed_Harrison. urticarial or papular rash called 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.


InternalMed_Harrison

InternalMed_Harrison. Several families of beetles have independently developed the ability to produce chemically unrelated vesicating toxins. When disturbed, blister beetles (family Meloidae) extrude cantharidin, a low-molecularweight toxin that produces thin-walled blisters (≤5 cm in diameter) 2–5 h after contact. The blisters are not painful or pruritic unless broken and resolve without treatment in ≤10 days. Nephritis may follow unusually heavy cantharidin exposure. Contact occurs when individuals sit on the ground, work in the garden, or deliberately handle the beetles. The hemolymph of certain rove beetles (Staphylinidae) 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


InternalMed_Harrison

InternalMed_Harrison. 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.


InternalMed_Harrison

InternalMed_Harrison. 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 as bites of bedbugs.


InternalMed_Harrison

InternalMed_Harrison. The groundless conviction that one is infested with arthropods or other parasites (Ekbom’s syndrome, delusory parasitosis, delusions of parasitosis, and perhaps Morgellons syndrome) is extremely difficult to treat and, unfortunately, is not uncommon. 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. When evaluating a patient with possible delusional parasitosis, it is imperative to rule out true infestations and bites by arthropods, endocrinopathies, sensory disorders due to neuropathies,


InternalMed_Harrison

InternalMed_Harrison. When evaluating 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 infested by a previously unknown pathogen, while their personal lives, 2751 sensations. Frequently, such patients repeatedly seek medical consulta-family support, and employment collapse around them. tions, 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 Acknowledgmentthan psychotherapy in treating this disorder. Patients with delusional The substantial contributions of Andrew Spielman and James H. parasitosis often develop the unshakeable conviction that they are Maguire to this chapter in previous editions are gratefully


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InternalMed_Harrison. delusional The substantial contributions of Andrew Spielman and James H. parasitosis often develop the unshakeable conviction that they are Maguire to this chapter in previous editions are gratefully acknowledged.


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InternalMed_Harrison. 476e-1 altitude Illness Buddha Basnyat, Geoffrey Tabin EPIDEMIOLOGY Mountains cover one-fifth of the earth’s surface; 38 million people live permanently at altitudes ≥2400 m, and 100 million people travel to high-altitude locations each year. Skiers in the Alps or Aspen; religious pilgrims to Lhasa or Kailash; trekkers and climbers to Kilimanjaro, Aconcagua, or Everest; and military personnel deployed ACUTE MOUNTAIN SICKNESS AND HIGH-ALTITUDE CEREBRAL EDEMA AMS is a neurologic syndrome characterized by nonspecific symp-toms (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. AMS must be distinguished from exhaustion, dehydration, hypothermia, alcoholic hangover, and hyponatremia. AMS and HACE are thought to represent oppo-site ends of a


InternalMed_Harrison

InternalMed_Harrison. Symposium, is generally used. AMS must be distinguished from exhaustion, dehydration, hypothermia, alcoholic hangover, and hyponatremia. AMS and HACE are thought to represent oppo-site 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 476e PART 19: Disorders Associated with Environmental Exposures 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


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InternalMed_Harrison. 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%.


InternalMed_Harrison

InternalMed_Harrison. 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 acclimation—mediated by the carotid bodies. Hyperventilation may cause respiratory alkalosis and dehydration. Alkalosis may depress the ventilatory drive during sleep, with consequent periodic breathing and hypoxemia. During early acclimation, 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 acclimation include increased sympathetic tone; increased erythropoietin levels, leading to increased hemoglobin levels and red blood cell mass; increased tissue capillary


InternalMed_Harrison

InternalMed_Harrison. changes during normal acclimation 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 acclimation, 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. Finally, if the ascent is made faster than the body can adapt to the stress of hypobaric hypoxemia, altitude-related disease states can result.


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InternalMed_Harrison. Hypoxia-inducible factor, which is important in high-altitude 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 hypoxia-inducible 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 the Han Chinese. For acute altitude illness, a single gene variant is unlikely to be found, but the 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. Approximately 58 candidate genes have been tested, and at least one variant from 17 of these genes is associated with altitude illness.


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InternalMed_Harrison. but generally without focal neurologic deficits. Progression to these signal manifestations can be rapid. Papilledema and, more commonly, retinal hemorrhages may also develop. In fact, retinal hemorrhages occur frequently at ≥5000 m, even in individuals without clinical symptoms of AMS or HACE. It is unclear whether retinal hemorrhage and cerebral hemorrhage at high altitude are caused by the same mechanism.


InternalMed_Harrison

InternalMed_Harrison. Risk Factors The most important risk factors for the development of altitude illness are the rate of ascent and a prior history of high-altitude 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. Aging appears to be associated with blunting of cardiac chronotropic function and an increase in ventilatory response leading to maintenance of arterial oxygen saturation in hypoxia. Most studies reveal no gender difference in AMS incidence. A recent study showed that, in women, adaptive responses to hypoxia with aging are blunted by menopause but can be maintained with endurance training. Sleep desaturation—a common phenomenon at high altitude—is associated


InternalMed_Harrison

InternalMed_Harrison. that, in women, adaptive responses to hypoxia with aging are blunted by menopause but can be maintained with endurance training. Sleep desaturation—a common phenomenon at high altitude—is associated with AMS. Debilitating fatigue consistent with severe AMS on descent from a summit is also an important risk factor for death in mountaineers. A recently published prospective study involving trekkers and climbers who ascended to altitudes between 4000 m 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 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


InternalMed_Harrison

InternalMed_Harrison. 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.


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InternalMed_Harrison. Pathophysiology The exact mechanisms causing 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 setting of high-altitude illness, the MRI findings shown in Fig. 476e-1 are confirmatory of HACE, with increased signal in the white matter and particularly in the splenium of the corpus callosum. Quantitative analysis in a 3-tesla 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.


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InternalMed_Harrison. 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 FIGURE 476e-1 T2 magnetic resonance image of the brain of a patient with high-altitude 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.


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InternalMed_Harrison. (With permission from Wilderness Environ Med 15:53–55, 2004.) in the brain at high altitude, and studies in mice have borne out this role. Although preliminary 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 calcium-mediated nitric oxide and neuronally mediated adenosine, which may promote cerebral vasodilation.


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InternalMed_Harrison. Increased sympathetic activity triggered by hypoxia may also contribute to blood-brain barrier leakage. Enhanced optic-nerve sheath diameter with increasing severity of AMS has been noted and suggests an important role for increased intracranial pressures in the pathophysiology of AMS. Microhemorrhage formation caused by cytokines or damage through increased hydrostatic pressure is an important feature of HACE. Lesions in the globus pallidum (which is sensitive to hypoxia) leading to Parkinson’s disease have also been reported to be complications of HACE. Finally, the effect of hypoxia on reactive oxygen species and the role of these species in clinical AMS are unclear.


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InternalMed_Harrison. 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. Although the International Headache Society acknowledges that high altitude may be a trigger for migraine, it is unclear whether high-altitude headache and migraine share the same pathophysiology.


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InternalMed_Harrison. Prevention and Treatment (Table 476e-1) Gradual ascent, with adequate time for acclimation, is the best method for the prevention of altitude illness. Even though there may be individual variation in the rate of acclimation, a graded ascent of ≤400 m from the previous day’s sleeping altitude is recommended above 3000 m, and taking every third day of gain in sleeping altitude as an extra day for acclimation is helpful. Spending one night at an intermediate altitude before proceeding to a higher altitude may enhance acclimation and attenuate the risk of AMS. Another protective factor in AMS is high-altitude exposure Acute mountain sickness Discontinuation of ascent (AMS), milda Treatment with acetazolamide (250 mg q12h) 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 Administration of oxygen (2–4 L/min)


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InternalMed_Harrison. Use of low-flow oxygen if available Treatment with acetazolamide (250 mg q12h) and/or dexamethasone (4 mg q6h)c 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 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, extended-release, q12h)


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InternalMed_Harrison. Adjunctive therapy with nifedipinee (30 mg, extended-release, q12h) Hyperbaric therapy if descent is not possible aCategorization 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, insomnia). bNo fixed altitude is specified; the patient should descend to a point below that at which symptoms developed. cAcetazolamide treats and dexamethasone masks symptoms. For prevention (as opposed to treatment), 125–250 mg of acetazolamide q12h or (when acetazolamide is contraindicated—e.g., in people with sulfa allergy) 4 mg of dexamethasone q12h may be used. dIn hyperbaric therapy, the patient is placed in a portable altitude chamber or bag to simulate descent. eNifedipine at this dose is also effective for the prevention of HAPE, as is salmeterol (125 mg inhaled twice daily), tadalafil (10 mg twice daily), or dexamethasone (8 mg twice daily).


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InternalMed_Harrison. 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 of ≥2000 m rather than with an ascent from sea level. Studies have examined whether exposure to a normobaric hypoxic environment (in a room or a tent) before an ascent can provide protection against AMS. In double-blind placebo-controlled trials, repeated intermittent exposure (60–90 min) to normobaric hypoxia (up to 4500 m) or continuous exposure to 3000 m during 8 h of sleep for 7 consecutive days failed to reduce the incidence of AMS at altitudes of 4300–4559 m.


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InternalMed_Harrison. 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. Finally, proper hydration (but not overhydration) in high-altitude trekking and climbing, aimed at countering fluid loss due to hyperventilation and sweating, may also 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 acclimation 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 a prompt bicarbonate diuresis that leads to metabolic acidosis and hyperventilation. Acetazolamide (125–250 mg twice a


InternalMed_Harrison

InternalMed_Harrison. drug of choice for AMS prevention. It inhibits renal carbonic anhydrase, causing a prompt bicarbonate diuresis that leads to metabolic acidosis and hyperventilation. Acetazolamide (125–250 mg twice a day), administered for 1 day before ascent and continued for 2 or 3 days, is effective. Higher doses are not required. A meta-analysis limited to randomized controlled trials revealed that 125 mg of acetazolamide twice daily was effective in the prevention of AMS, with a relative-risk reduction of ~48% from values obtained with placebo. Paresthesia and a tingling sensation are common side effects of acetazolamide. This drug is a nonantibiotic sulfonamide that has low-level cross-reactivity with sulfa antibiotics; as a result, severe reactions are rare. Dexamethasone (8 mg/d in divided doses) is also effective. A large-scale, randomized, double-blind, placebo-controlled trial in partially acclimated trekkers has clearly shown that Ginkgo biloba is ineffective in the prevention of AMS.


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InternalMed_Harrison. is also effective. A large-scale, randomized, double-blind, placebo-controlled trial in partially acclimated trekkers has clearly shown that Ginkgo biloba is ineffective in the prevention of AMS. Recently, ibuprofen (600 mg three times daily) was shown to be beneficial in the prevention of AMS, but more definitive studies and proper gastrointestinal-bleeding risk assessment need to be conducted before ibuprofen can be routinely recommended for AMS prevention. Many drugs, including spironolactone, medroxyprogesterone, magnesium, calcium channel blockers, and antacids, confer no benefit in the prevention of AMS. Similarly, no efficacy studies are available for coca leaves (a weak form of cocaine), which are offered to high-altitude travelers in the Andes, or for soroche pills, which contain aspirin, caffeine, and acetaminophen and are sold over the counter in Bolivia and Peru. Finally, a word of caution applies in the pharmacologic prevention of altitude illness. A fast-growing


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InternalMed_Harrison. contain aspirin, caffeine, and acetaminophen and are sold over the counter in Bolivia and Peru. Finally, a word of caution applies in the pharmacologic prevention of altitude illness. A fast-growing population of climbers in pursuit of a summit are using prophylactic drugs such as glucocorticoids in an attempt to improve their performance; the outcome can be tragic because of potentially severe side effects of these drugs.


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InternalMed_Harrison. For the treatment of mild AMS, rest alone with analgesic use may be adequate. Descent and the use of acetazolamide and (if available) oxygen are sufficient to treat most cases of moderate AMS. Even a minor descent (400–500 m) may be adequate for symptom relief. For moderate AMS or early HACE, dexamethasone (4 mg orally or parenterally) is highly effective. For HACE, immediate descent is mandatory. When descent is not possible because of poor weather conditions or darkness, a simulation of descent in a portable hyperbaric chamber is effective and, like dexamethasone administration, “buys time.” Thus, in certain high-altitude locations (e.g., remote pilgrimage sites), the decision to bring along the light-weight hyperbaric chamber may prove lifesaving. Like nifedipine, phosphodiesterase-5 inhibitors have no role in the treatment of AMS or HACE.


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InternalMed_Harrison. HIGH-ALTITUDE PULMONARY EDEMA Risk Factors and Manifestations Unlike HACE (a neurologic disorder), HAPE is primarily a pulmonary problem and therefore is not necessarily preceded by AMS. HAPE develops within 2–4 days after arrival at high altitude; it rarely occurs after more than 4 or 5 days at the same altitude, probably because of remodeling and adaptation that render the pulmonary vasculature less susceptible to the effects of hypoxia. A rapid rate of ascent, a history of HAPE, respiratory tract infections, and cold environmental temperatures are risk factors. Men are more susceptible than women. People with abnormalities of the cardiopulmonary circulation leading to pulmonary hypertension—e.g., large patent foramen ovale, mitral stenosis, primary pulmonary hypertension, and unilateral absence of the pulmonary artery—are at increased risk of HAPE, even at moderate altitudes. For example, patent foramen ovale is four times more common among HAPE-susceptible individuals than in the


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InternalMed_Harrison. absence of the pulmonary artery—are at increased risk of HAPE, even at moderate altitudes. For example, patent foramen ovale is four times more common among HAPE-susceptible individuals than in the general population. Echocardiography is recommended when HAPE develops at relatively low altitudes (<3000 m) and whenever cardiopulmonary abnormalities predisposing to HAPE are suspected.


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InternalMed_Harrison. The initial manifestation of HAPE may be a reduction in exercise tolerance greater than that expected at the given altitude. Although a dry, persistent cough may presage HAPE and may be followed by the production of blood-tinged sputum, cough in the mountains is almost universal and the mechanism is poorly understood. Tachypnea and tachycardia, even at rest, are important markers as illness progresses. Crackles may be heard on auscultation but are not diagnostic. HAPE may be accompanied by signs of HACE. Patchy or localized opacities (Fig. 476e-2) or streaky interstitial edema may be noted on chest radiography. In the past, HAPE was mistaken for pneumonia due to the cold or for heart failure due to hypoxia and exertion. Kerley B lines or a bat-wing appearance are not seen on radiography. Electrocardiography may reveal right ventricular strain or even hypertrophy. Hypoxemia and respiratory alkalosis are consistently present unless the patient is taking acetazolamide, in which case


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InternalMed_Harrison. Electrocardiography may reveal right ventricular strain or even hypertrophy. Hypoxemia and respiratory alkalosis are consistently present unless the patient is taking acetazolamide, in which case metabolic acidosis may supervene. Assessment of arterial blood gases is not necessary in the evaluation of HAPE; an oxygen saturation reading with a pulse oximeter is generally adequate. The existence of a subclinical form of HAPE has been suggested by an increased alveolar-arterial oxygen gradient in Everest


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InternalMed_Harrison. FIGURE 476e-2 Chest radiograph of a patient with high-altitude pulmonary edema shows opacity in the right middle and lower zones simulating pneumonic consolidation. The opacity cleared almost completely in 2 days with descent and supplemental oxygen. climbers near the summit, but hard evidence correlating this abnormality with the development of clinically relevant HAPE is lacking.


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InternalMed_Harrison. Pathophysiology HAPE is a noncardiogenic pulmonary edema characterized by patchy pulmonary vasoconstriction that leads to over-perfusion in some areas. This abnormality leads in turn to increased pulmonary capillary pressure (>18 mmHg) and capillary “stress” failure. The exact mechanism for the vasoconstriction is unknown. Endothelial dysfunction due to hypoxia may play a role by impairing the release of nitric oxide, an endothelium-derived vasodilator. At high altitude, HAPE-prone persons have reduced levels of exhaled nitric oxide. The effectiveness of phosphodiesterase-5 inhibitors in alleviating altitude-induced pulmonary hypertension, decreased exercise tolerance, and hypoxemia supports the role of nitric oxide in the pathogenesis of HAPE. One study demonstrated that prophylactic use of tadalafil, a phosphodiesterase-5 inhibitor, decreases the risk of HAPE by 65%. In contrast, the endothelium also synthesizes endothelin-1, a potent vasoconstrictor whose concentrations are higher


InternalMed_Harrison

InternalMed_Harrison. of tadalafil, a phosphodiesterase-5 inhibitor, decreases the risk of HAPE by 65%. In contrast, the endothelium also synthesizes endothelin-1, a potent vasoconstrictor whose concentrations are higher than average in HAPE-prone mountaineers. Bosentan, an endothelin receptor antagonist, attenuates hypoxia-induced pulmonary hypertension, but further field studies with this drug are necessary.


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InternalMed_Harrison. Exercise and cold lead to increased pulmonary intravascular pressure and may predispose to HAPE. In addition, hypoxia-triggered increases in sympathetic drive may lead to pulmonary venoconstriction and extravasation into the alveoli from the pulmonary capillaries. Consistent with this concept, phentolamine, which elicits α-adrenergic blockade, improves hemodynamics and oxygenation in HAPE more than do other vasodilators. The study of tadalafil cited above also investigated dexamethasone in the prevention of HAPE. Surprisingly, dexamethasone reduced the incidence of HAPE by 78%—a greater decrease than with tadalafil. Besides possibly increasing the availability of endothelial nitric oxide, dexamethasone may have altered the excessive sympathetic activity associated with HAPE: the heart rate of participants in the dexamethasone arm of the study was significantly lowered. Finally, people susceptible to HAPE also display enhanced sympathetic activity during short-term hypoxic breathing at


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InternalMed_Harrison. of participants in the dexamethasone arm of the study was significantly lowered. Finally, people susceptible to HAPE also display enhanced sympathetic activity during short-term hypoxic breathing at low altitudes.


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InternalMed_Harrison. Because many patients with HAPE have fever, peripheral leukocytosis, and an increased erythrocyte sedimentation rate, inflammation has been considered an etiologic factor in HAPE. However, strong evidence suggests that inflammation in HAPE is an epiphenomenon rather than the primary cause. Nevertheless, inflammatory processes (e.g., those elicited by viral respiratory tract infections) do predispose persons to HAPE—even those who are constitutionally resistant to its development.


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InternalMed_Harrison. Another proposed mechanism for HAPE is impaired transepithelial clearance of sodium and water from the alveoli. β-Adrenergic agonists upregulate the clearance of alveolar fluid in animal models. In a double-blind, randomized, placebo-controlled study of HAPE-susceptible mountaineers, prophylactic inhalation of the β-adrenergic agonist salmeterol reduced the incidence of HAPE by 50%. Other effects of β agonists may also contribute to the prevention of HAPE, but these findings are in keeping with the concept that alveolar fluid clearance may play a pathogenic role in this illness.


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InternalMed_Harrison. Prevention and Treatment (Table 476e-1) Allowing sufficient time for acclimation by ascending gradually (as discussed above for AMS and HACE) is the best way to prevent HAPE. Sustained-release nifedipine (30 mg), given once or twice daily, prevents HAPE in people who must ascend rapidly or who have a history of HAPE. Other drugs for the prevention of HAPE are listed in Table 476e-1 (footnote e). Although dexamethasone is listed for prevention, its adverse-effect profile requires close monitoring. Acetazolamide has been shown to blunt hypoxic pulmonary vasoconstriction in animal models, and this observation warrants further study in HAPE prevention. However, one large study failed to show a decrease in pulmonary vasoconstriction in partially acclimated individuals given acetazolamide.


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InternalMed_Harrison. Early recognition is paramount in the treatment of HAPE, especially when it is not preceded by the AMS symptoms of headache and nausea. Fatigue and dyspnea at rest may be the only initial manifestations. Descent and the use of supplementary oxygen (aimed at bringing oxygen saturation to >90%) are the most effective therapeutic interventions. Exertion should be kept to a minimum, and the patient should be kept warm. Hyperbaric therapy in a portable altitude chamber may be used if descent is not possible and oxygen is not available. Oral sustained-release nifedipine (30 mg once or twice daily) can be used as adjunctive therapy. Inhaled β agonists, which are safe and convenient to carry, are useful in the prevention of HAPE and may be effective in its treatment, although no trials have yet been carried out. Inhaled nitric oxide and expiratory positive airway pressure may also be useful therapeutic measures but may not be available in high-altitude settings. No studies have investigated


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InternalMed_Harrison. been carried out. Inhaled nitric oxide and expiratory positive airway pressure may also be useful therapeutic measures but may not be available in high-altitude settings. No studies have investigated phosphodiesterase-5 inhibitors in the treatment of HAPE, but reports have described their use in clinical practice. The mainstays of treatment remain descent and (if available) oxygen.


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InternalMed_Harrison. In AMS, if symptoms abate (with or without acetazolamide), the patient may reascend gradually to a higher altitude. Unlike that in acute respiratory distress syndrome (another noncardiogenic pulmonary edema), the architecture of the lung in HAPE is usually well preserved, with rapid reversibility of abnormalities (Fig. 476e-2). This fact has allowed some people with HAPE to reascend slowly after a few days of descent and rest. In HACE, reascent after a few days may not be advisable during the same trip.


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InternalMed_Harrison. OTHER HIGH-ALTITUDE PROBLEMS Sleep Impairment The mechanisms underlying sleep problems, which are among the most common adverse reactions to high altitude, include increased periodic breathing; changes in sleep architecture, with increased time in lighter sleep stages; and changes in rapid eye movement sleep. Sojourners should be reassured that sleep quality improves with acclimation. In cases where drugs do need to be used, acetazolamide (125 mg before bedtime) is especially useful because this agent decreases hypoxemic episodes and alleviates sleeping disruptions caused by excessive periodic breathing. Whether combining acetazolamide with temazepam or zolpidem is more effective than administering acetazolamide alone is unknown. In combinations, the doses of temazepam and zolpidem should not be increased by >10 mg at high altitudes. Limited evidence suggests that diazepam causes hypoventilation at high altitudes and therefore is contraindicated. For trekkers with obstructive sleep


InternalMed_Harrison

InternalMed_Harrison. not be increased by >10 mg at high altitudes. Limited evidence suggests that diazepam causes hypoventilation at high altitudes and therefore is contraindicated. For trekkers with obstructive sleep apnea who are using a continuous positive airway pressure (CPAP) machine, the addition of acetazolamide, which will decrease centrally mediated sleep apnea, may be helpful. There is evidence to show that obstructive sleep apnea at high altitude may decrease and “convert” to central sleep apnea.


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InternalMed_Harrison. Gastrointestinal Issues High-altitude exposure may be associated with increased gastric and duodenal bleeding, but further studies are required to determine whether there is a causal effect. Because of decreased atmospheric pressure and consequent intestinal gas expansion at high altitudes, many sojourners experience abdominal bloating and distension as well as excessive flatus expulsion. In the absence of diarrhea, these phenomena are normal, if sometimes uncomfortable. Accompanying diarrhea, however, may indicate the involvement of bacteria or Giardia parasites, which are common at many high-altitude locations in the developing world. Prompt treatment with fluids and empirical antibiotics may be required to combat dehydration in the mountains. Finally, hemorrhoids are common on high-altitude treks; treatment includes hot soaks, application of hydrocortisone ointment, and measures to avoid constipation.


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InternalMed_Harrison. High-Altitude Cough High-altitude cough can be debilitating and is sometimes severe enough to cause rib fracture, especially at >5000 m. The etiology is probably multifactorial. Although high-altitude cough has been attributed to inspiration of cold dry air, this explanation appears not to be sufficient by itself; in long-duration studies in hypobaric chambers, cough has occurred despite controlled temperature and humidity. The implication is that hypoxia also plays a role. Exercise can precipitate cough at high altitudes, possibly because of water loss from the respiratory tract. Long-acting β agonists and glucocorticoids prevent bronchoconstriction that otherwise may be brought on by cold and exercise. In general, infection does not seem to be a common etiology. Anecdotal reports have described the efficacy of an inhaled combination of fluticasone and salmeterol in the treatment of high-altitude cough; however, a placebo-controlled, randomized trial failed to support this beneficial


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InternalMed_Harrison. the efficacy of an inhaled combination of fluticasone and salmeterol in the treatment of high-altitude cough; however, a placebo-controlled, randomized trial failed to support this beneficial effect. Furthermore, anecdotal evidence supports the utility of the proton pump inhibitor omeprazole in preventing gastroesophageal reflux in some trekkers and climbers. In most situations, cough resolves upon descent.


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InternalMed_Harrison. High-Altitude Neurologic Events Unrelated to “Altitude Illness” Transient ischemic attacks (TIAs) and strokes have been well described in high-altitude sojourners outside the setting of altitude sickness. However, these descriptions are not based on cause (hypoxia) and effect. In general, symptoms of AMS present gradually, whereas many of these neurologic events happen suddenly. The population that suffers strokes and TIAs at sea level is generally an older age group with other risk factors, whereas those so afflicted at high altitudes are generally younger and probably have fewer risk factors for atherosclerotic vascular disease. Other mechanisms (e.g., migraine, vasospasm, focal edema, hypocapneic vasoconstriction, hypoxia in the watershed zones of minimal cerebral blood flow, or cardiac right-to-left shunt) may be operative in TIAs and strokes at high altitude.


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InternalMed_Harrison. Subarachnoid hemorrhage, transient global amnesia, delirium, and cranial nerve palsies (e.g., lateral rectus palsy) occurring at high altitudes but outside the setting of altitude sickness have also been well described. Syncope is common at moderately high altitudes, generally occurs shortly after ascent, usually resolves without descent, and appears to be a vasovagal event related to hypoxemia. Seizures occur rarely with HACE, but hypoxemia and hypocapnia, which are prevalent at high altitudes, are well-known triggers that may contribute to new or breakthrough seizures in predisposed individuals. Nevertheless, the consensus among experts is that sojourners with well-controlled seizure disorders can ascend to high altitudes. Ophthalmologic problems, such as cortical blindness, amaurosis fugax, and retinal hemorrhage with macular involvement and compromised vision, are well recognized. Visual problems from previous refractive surgery and blurred monocular vision—due either to the use


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InternalMed_Harrison. fugax, and retinal hemorrhage with macular involvement and compromised vision, are well recognized. Visual problems from previous refractive surgery and blurred monocular vision—due either to the use of a transdermal scopolamine patch (touching the eye after touching the patch) or to dry-eye syndrome—may also occur in the field at high altitudes and may be confused with neurologic conditions. Finally, persons with hypercoagulable conditions (e.g., antiphospholipid syndrome, protein C deficiency) who are asymptomatic at sea level may experience cerebral venous thrombosis (possibly due to the enhanced blood viscosity triggered by polycythemia and dehydration) at high altitudes. Proper history taking, examination, and prompt investigations where possible will help define these conditions as entities separate from altitude sickness. Administration of oxygen (where available) and prompt descent are the cornerstones of treatment of most of these neurologic conditions.


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InternalMed_Harrison. Psychological/Psychiatric Problems Delirium characterized by a sudden change in mental status, a short attention span, disorganized thinking, and an agitated state during the period of confusion has been well described in mountain climbers and trekkers without a prior history. In addition, anxiety attacks, often triggered at night by excessive periodic breathing, are well documented. The contribution of hypoxia to these conditions is unknown. Expedition medical kits need to include antipsychotic injectable drugs to control psychosis in patients in remote high-altitude locations.


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InternalMed_Harrison. Because travel to high altitudes is increasingly popular, common conditions such as hypertension, coronary artery disease, and diabetes are more frequently encountered among high-altitude sojourners. This situation is of particular concern for the thousands of elderly pilgrims with medical problems who visit high-altitude sacred areas (e.g., in the Himalayas) each year. In recent years, high-altitude travel has attracted intrepid trekkers who are taking immunosuppressive medications (e.g., kidney transplant recipients or patients undergoing chemotherapy). Recommended vaccinations and other precautions (e.g., hand washing) may be especially important for this group. Although most of these medical conditions do not appear to influence susceptibility to altitude illness, they may be exacerbated by ascent to altitude, exertion in cold conditions, and hypoxemia. Advice regarding the advisability of high-altitude travel and the impact of high-altitude hypoxia on these preexisting conditions


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InternalMed_Harrison. by ascent to altitude, exertion in cold conditions, and hypoxemia. Advice regarding the advisability of high-altitude travel and the impact of high-altitude hypoxia on these preexisting conditions is becoming increasingly relevant, but there are no evidence-based guidelines. In addition, recommendations made for relatively low altitudes (~3000 m) may not hold true for higher altitudes (>4000 m), where hypoxic stress is greater. Personal risks and benefits must be clearly thought through before ascent.