Environmental Dermatology

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Clinical Presentation

Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.¹ On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.² Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.² The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.^3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.⁵

Diagnostic Difficulties

Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.^2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.² The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.

Conclusion

Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.

Incidence and Characteristics

Stingrays are the most common cause of fish-related stings worldwide.¹ The Urolophidae and Dasyatidae stingray families are responsible for most marine stingray injuries, including approximately 1500 reported injuries in the United States annually.^1,2 Saltwater stingrays from these families commonly are encountered in shallow temperate and tropical coastal waters across the globe and possess dorsally and distally located spines capable of injuring humans that step on them (Figure 1).^1,3 Freshwater stingrays (Potamotrygonidae family)(Figure 2) are not present in North America but rather inhabit lakes and river systems in South America, Africa, Laos, and Vietnam.⁴ Although recent incidence is unknown, Marinkelle⁵ estimated that thousands of stingray injuries occurred annually in the freshwater of Columbia during the 1960s. Unfortunately, the annual worldwide incidence of stingray injuries is generally unknown and is difficult to estimate, in part because injuries often go unreported.

Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.³ Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.^6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.

Injury Clinical Presentation

Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.⁸ Fishermen can present with injuries of the upper extremities after handling fish with their hands.⁹ Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.^10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.^1,8,12,13

Management

Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.^8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.⁸ In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.⁹ In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.^8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.^9,15

Infection
One major complication of stingray injuries is infection.^8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.^8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.¹⁸ Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.¹⁹

Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.^8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.^1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.¹³ Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.²⁰ Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.²¹ Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.

Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.^3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.^23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.^1,24

Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al⁹ found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.³ However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.^2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.^2,9

Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.²¹

Avoidance and Prevention

Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.²⁶ Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.²⁶ Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.

Incidence and Characteristics

Stingrays are the most common cause of fish-related stings worldwide.¹ The Urolophidae and Dasyatidae stingray families are responsible for most marine stingray injuries, including approximately 1500 reported injuries in the United States annually.^1,2 Saltwater stingrays from these families commonly are encountered in shallow temperate and tropical coastal waters across the globe and possess dorsally and distally located spines capable of injuring humans that step on them (Figure 1).^1,3 Freshwater stingrays (Potamotrygonidae family)(Figure 2) are not present in North America but rather inhabit lakes and river systems in South America, Africa, Laos, and Vietnam.⁴ Although recent incidence is unknown, Marinkelle⁵ estimated that thousands of stingray injuries occurred annually in the freshwater of Columbia during the 1960s. Unfortunately, the annual worldwide incidence of stingray injuries is generally unknown and is difficult to estimate, in part because injuries often go unreported.

Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.³ Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.^6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.

Injury Clinical Presentation

Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.⁸ Fishermen can present with injuries of the upper extremities after handling fish with their hands.⁹ Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.^10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.^1,8,12,13

Management

Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.^8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.⁸ In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.⁹ In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.^8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.^9,15

Infection
One major complication of stingray injuries is infection.^8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.^8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.¹⁸ Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.¹⁹

Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.^8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.^1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.¹³ Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.²⁰ Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.²¹ Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.

Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.^3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.^23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.^1,24

Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al⁹ found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.³ However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.^2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.^2,9

Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.²¹

Avoidance and Prevention

Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.²⁶ Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.²⁶ Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.

Incidence and Characteristics

Stingrays are the most common cause of fish-related stings worldwide.¹ The Urolophidae and Dasyatidae stingray families are responsible for most marine stingray injuries, including approximately 1500 reported injuries in the United States annually.^1,2 Saltwater stingrays from these families commonly are encountered in shallow temperate and tropical coastal waters across the globe and possess dorsally and distally located spines capable of injuring humans that step on them (Figure 1).^1,3 Freshwater stingrays (Potamotrygonidae family)(Figure 2) are not present in North America but rather inhabit lakes and river systems in South America, Africa, Laos, and Vietnam.⁴ Although recent incidence is unknown, Marinkelle⁵ estimated that thousands of stingray injuries occurred annually in the freshwater of Columbia during the 1960s. Unfortunately, the annual worldwide incidence of stingray injuries is generally unknown and is difficult to estimate, in part because injuries often go unreported.

Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.³ Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.^6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.

Injury Clinical Presentation

Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.⁸ Fishermen can present with injuries of the upper extremities after handling fish with their hands.⁹ Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.^10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.^1,8,12,13

Management

Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.^8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.⁸ In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.⁹ In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.^8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.^9,15

Infection
One major complication of stingray injuries is infection.^8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.^8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.¹⁸ Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.¹⁹

Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.^8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.^1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.¹³ Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.²⁰ Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.²¹ Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.

Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.^3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.^23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.^1,24

Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al⁹ found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.³ However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.^2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.^2,9

Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.²¹

Avoidance and Prevention

Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.²⁶ Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.²⁶ Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

 

 

Discussion

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

 

 

Discussion

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

Bedbugs are common pests causing several health and economic consequences. With increased travel, pesticide resistance, and a lack of awareness about prevention, bedbugs have become even more difficult to control, especially within large population centers.¹ The US Environmental Protection Agency considers bedbugs to be a considerable public health issue.² Typically, they are found in private residences; however, there have been more reports of bedbugs discovered in the workplace within the last 20 years.^3-5 Herein, we present a case of bedbugs presenting in this unusual environment.

Case Report

A 42-year-old man presented to our dermatology clinic with intensely itchy bumps over the bilateral posterior arms of 3 months’ duration. He had no other skin, hair, or nail concerns. Over the last 3 months prior to dermatologic evaluation, he was treated by an outside physician with topical steroids, systemic antibiotics, topical antifungals, and even systemic steroids with no improvement of the lesions or symptoms. On clinical examination at the current presentation, 8 to 10 pink dermal papules coalescing into 10-cm round patches were noted on the bilateral posterior arms (Figure 1). A punch biopsy of the posterior right arm was performed, and histologic analysis showed a dense superficial and deep infiltrate and a perivascular infiltrate of lymphocytes and eosinophils (Figure 2). No notable epidermal changes were observed.

At this time, the patient was counseled that the most likely cause was some unknown arthropod exposure. Given the chronicity of the patient’s disease course, bedbugs were favored; however, an extensive search of the patient’s home failed to uncover any arthropods, let alone bedbugs. A few weeks later, the patient discovered insects emanating from the mesh backing of his office chair while at work (Figure 3). The location of the intruders corresponded exactly with the lesions on the posterior arms. The occupational health office at his workplace collected samples of the arthropods and confirmed they were bedbugs. The patient’s lesions resolved with topical clobetasol once eradication of the workplace was complete.

 

 

Discussion

Morphology and Epidemiology
Bedbugs are wingless arthropods that have flat, oval-shaped, reddish brown bodies. They are approximately 4.5-mm long and 2.5-mm wide (Figure 4). The 2 most common species of bedbugs that infect humans are Cimex lectularius and Cimex hemipterus. Bedbugs are most commonly found in hotels, apartments, and residential households near sleep locations. They reside in crevices, cracks, mattresses, cushions, dressers, and other structures proximal to the bed. During the day they remain hidden, but at night they emerge for a blood meal. The average lifespan of a bedbug is 6 to 12 months.⁶ Females lay more than 200 eggs that hatch in approximately 6 to 10 days.⁷ Bedbugs progress through 5 nymph stages before becoming adults; several blood meals are required to advance each stage.⁶

Although commonly attributed to the home, bedbugs are being increasingly seen in the office setting.^3-5 In a survey given to pest management professionals in 2015, more than 45% reported that they were contracted by corporations for bedbug infestations in office settings, an increase from 18% in 2010 and 36% in 2013.³ Bedbugs are brought into offices through clothing, luggage, books, and other personal items. Unable to find hosts at night, bedbugs adapt to daytime hours and spread to more unpredictable locations, including chairs, office equipment, desks, and computers.⁴ Additionally, they frequently move around to find a suitable host.⁵ As a result, the growth rate of bedbugs in an office setting is much slower than in the home, with fewer insects. Our patient did not have bedbugs at home, but it is possible that other employees transported them to the office over time.

Clinical Manifestations
Bedbugs cause pruritic and nonpruritic skin rashes, often of the arms, legs, neck, and face. A common reaction is an erythematous papule with a hemorrhagic punctum caused by one bite.⁸ Other presentations include purpuric macules, bullae, and papular urticaria.^8-10 Although bedbugs are suspected to transmit infectious diseases, no reports have substantiated that claim.¹¹

Our patient had several coalescing dermal papules on the arms indicating multiple bites around the same area. Due to the stationary aspect of his job—with the arms resting on his chair while typing at his desk—our patient was an easy target for consistent blood meals.

Detection
Due to an overall smaller population of insects in an office setting, detection of bedbugs in the workplace can be difficult. Infestations can be primarily identified on visual inspection by pest control.¹² The mesh backing on our patient’s chair was one site where bedbugs resided. It is important to check areas where employees congregate, such as lounges, lunch areas, conference rooms, and printers.⁴ It also is essential to examine coatracks and locker rooms, as employees may leave personal items that can serve as a source of transmission of the bugs from home. Additional detection tools provided by pest management professionals include canines, as well as devices that emit pheromones, carbon dioxide, or heat to ensnare the insects.¹²

Treatment
Treatment of bedbug bites is quite variable. For some patients, lesions may resolve on their own. Pruritic maculopapular eruptions can be treated with topical pramoxine or doxepin.⁸ Patients who develop allergic urticaria can use oral antihistamines. Systemic reactions such as anaphylaxis can be treated with a combination of intramuscular epinephrine, antihistamines, and corticosteroids.⁸ The etiology of our patient’s condition initially was unknown, and thus he was given unnecessary systemic steroids and antifungals until the source of the rash was identified and eradicated. Topical clobetasol was subsequently administered and was sufficient to resolve his symptoms.

Final Thoughts

Bedbugs continue to remain a nuisance in the home. This case provides an example of bedbugs in the office, a location that is not commonly associated with bedbug infestations. Bedbugs pose numerous psychological, economic, and health consequences.² Productivity can be reduced, as patients with symptomatic lesions will be unable to work effectively, and those who are unaffected may be unwilling to work knowing their office environment poses a health risk. In addition, employees may worry about bringing the bedbugs home. It is important that employees be educated on the signs of a bedbug infestation and take preventive measures to stop spreading or introducing them to the office space. Due to the scattered habitation of bedbugs in offices, pest control managers need to be vigilant to identify sources of infestation and eradicate accordingly. Clinical manifestations can be nonspecific, resembling autoimmune disorders, fungal infections, or bites from other various arthropods; thus, treatment is highly dependent on the patient’s history and occupational exposure.

Bedbugs have successfully adapted to a new environment in the office space. Dermatologists and other health care professionals can no longer exclusively associate bedbugs with the home. When the clinical and histological presentation suggests an arthropod assault, we must counsel our patients to surveil their homes and work settings alike. If necessary, they should seek the assistance of occupational health professionals.

The lionfish (Pterois volitans) is a member of the Scorpaenidae family of venomous fish.^1-3 Lionfish are an invasive species originally from the Indian and Pacific oceans and the Red Sea that now are widely found throughout tropical and temperate oceans in both hemispheres. They are a popular aquarium fish and were inadvertently introduced in the Atlantic Ocean in South Florida during the late 1980s to early 1990s.^2,4 Since then, lionfish have spread into reef systems throughout the Atlantic Ocean, Caribbean Sea, and Gulf of Mexico in rapidly growing numbers, and they are now fo und all along the southeastern coast of the United States.⁵

Characteristics

Lionfish are brightly colored with red or maroon and white stripes, tentacles above the eyes and mouth, fan-shaped pectoral fins, and spines that deliver an especially painful venomous sting that often results in edema (Figure 1). They have 12 dorsal spines, 2 pelvic spines, and 3 anal spines.

Symptoms of Envenomation

As lionfish continue to spread to popular areas of the southeast Atlantic Ocean and Caribbean Sea, the chances of human contact with lionfish have increased. Lionfish stings are now the second most common marine envenomation injury after those caused by stingrays.⁴ Lionfish stings usually occur on the hands, fingers, or forearms during handling of the fish in ocean waters or in maintenance of aquariums. The mechanism of the venom apparatus is similar for all venomous fish. The spines have surrounding integumentary sheaths containing venom that rupture and inject venom when they penetrate the skin.⁶ The venom is a heat-labile neuromuscular toxin that causes edema (Figure 2), plasma extravasation, and thrombotic skin lesions.⁷

Wounds are classified into 3 categories: grade I consists of local erythema/ecchymosis, grade II involves vesicle or blister formation, and grade III denotes wounds that develop local necrosis.⁸ The sting causes immediate and severe throbbing pain, often described as excruciating or rated 10/10 on a basic pain scale, typically radiating up the affected limb. Puncture sites may bleed and often have associated redness and swelling. Pain may last up to 24 hours. Occasionally, foreign material may be left in the wound requiring removal. There also is a chance of secondary infection at the wound site, and severe envenomation can lead to local tissue necrosis.⁸ Systemic effects can occur in some cases, including nausea, vomiting, sweating, headache, dizziness, disorientation, palpitations, and even syncope.⁹ However, to our knowledge there are no documented cases of human death from a lionfish sting. Anaphylactic reactions are possible and require immediate treatment.⁶

A study conducted in the French West Indies evaluated 117 patients with lionfish envenomation and found that victims experienced severe pain and local edema (100%), paresthesia (90%), abdominal cramps (62%), extensive edema (53%), tachycardia (34%), skin rash (32%), gastrointestinal tract symptoms (28%), syncope (27%), transient weakness (24%), hypertension (21%), hypotension (18%), and hyperthermia (9%).⁹ Complications included local infection (18%) such as skin abscess (5%), skin necrosis (3%), and septic arthritis (2%). Twenty-two percent of patients were hospitalized and 8% required surgery. Local infectious complications were more frequent in those with multiple stings (19%). The study concluded that lionfish now represent a major health threat in the West Indies.⁹ As lionfish numbers have grown, health care providers are seeing increasing numbers of envenomation cases in areas of the coastal southeastern United States and Caribbean associated with considerable morbidity. Providers in nonendemic areas also may see envenomation injuries due to the lionfish popularity in home aquariums.⁹

Management

Individuals with lionfish stings should immerse the affected area in hot but not scalding water. Those with more serious injuries should seek medical attention. Home remedies that are generally contraindicated include application of topical papain or meat tenderizer.¹⁰ Data on ice packs are mixed, but because the toxin is heat labile, the most effective initial step in treatment is immersion of the affected area in water (temperature, 40°C to 45°C) for 30 to 90 minutes.⁶ The hot water inactivates the heat-labile toxin, leading to near-complete symptomatic relief in 80% of cases and moderate relief in an additional 14%. Immersion time more than 90 minutes considerably increases the risk for burns. Children should always be monitored to prevent burns. If a patient has received a nerve block for analgesia, the wound should not be immersed in hot water to avoid burns to the skin. The wound should be meticulously cleaned with saline irrigation, and radiography or ultrasonography should be performed as deemed necessary to look for any retained foreign bodies.⁸ Patients may require parenteral or oral analgesia as well as careful follow-up to ensure proper healing.⁹ Systemic symptoms require supportive care. Venomous fish wounds typically are small and superficial. Empiric antibiotic therapy is not advised for superficial wounds but may be required for clinically infected wounds.⁸ Tetanus prophylaxis should be given as appropriate to all affected patients. It has been noted that blister fluid contains high concentrations of lionfish venom, and when present, it increases the likelihood of converting the injury from a grade II to grade III wound with tissue necrosis; therefore, blisters should be drained or excised to decrease the chances of subsequent tissue necrosis.^11,12 If secondary infection such as cellulitis develops, antibiotics should be chosen to cover likely pathogens including common skin flora such as staphylococci and marine organisms such as Vibrio species. Wounds showing signs of infection should be cultured, with antibiotics adjusted according to sensitivities.⁵ Deeper wounds should be left open (unsutured) with a proper dressing to heal. Any wounds that involve vascular or joint structures require specialty management. Wounds involving joints may on occasion require surgical exploration and debridement.

Public Health Concerns

In an attempt to slow the growth of their population, human consumption of the fish has been encouraged. The lionfish toxin is inactivated by cooking, and the fish is considered a delicacy; however, a study in the Virgin Islands found that in areas with endemic ciguatera poisoning, 12% of lionfish carried amounts of the toxin above the level considered safe for consumption. This toxin is not inactivated by cooking or freezing and can lead to ciguatera fish poisoning for which there is no antidote and can be associated with prolonged neurotoxicity.¹³

Conclusion

As lionfish numbers continue to increase, physicians across multiple specialties and regions may see an increase in envenomation injuries. It is important that physicians are aware of how to recognize and treat lionfish stings, as prompt and comprehensive treatment provides benefit to the patient.

The lionfish (Pterois volitans) is a member of the Scorpaenidae family of venomous fish.^1-3 Lionfish are an invasive species originally from the Indian and Pacific oceans and the Red Sea that now are widely found throughout tropical and temperate oceans in both hemispheres. They are a popular aquarium fish and were inadvertently introduced in the Atlantic Ocean in South Florida during the late 1980s to early 1990s.^2,4 Since then, lionfish have spread into reef systems throughout the Atlantic Ocean, Caribbean Sea, and Gulf of Mexico in rapidly growing numbers, and they are now fo und all along the southeastern coast of the United States.⁵

Characteristics

Lionfish are brightly colored with red or maroon and white stripes, tentacles above the eyes and mouth, fan-shaped pectoral fins, and spines that deliver an especially painful venomous sting that often results in edema (Figure 1). They have 12 dorsal spines, 2 pelvic spines, and 3 anal spines.

Symptoms of Envenomation

As lionfish continue to spread to popular areas of the southeast Atlantic Ocean and Caribbean Sea, the chances of human contact with lionfish have increased. Lionfish stings are now the second most common marine envenomation injury after those caused by stingrays.⁴ Lionfish stings usually occur on the hands, fingers, or forearms during handling of the fish in ocean waters or in maintenance of aquariums. The mechanism of the venom apparatus is similar for all venomous fish. The spines have surrounding integumentary sheaths containing venom that rupture and inject venom when they penetrate the skin.⁶ The venom is a heat-labile neuromuscular toxin that causes edema (Figure 2), plasma extravasation, and thrombotic skin lesions.⁷

Wounds are classified into 3 categories: grade I consists of local erythema/ecchymosis, grade II involves vesicle or blister formation, and grade III denotes wounds that develop local necrosis.⁸ The sting causes immediate and severe throbbing pain, often described as excruciating or rated 10/10 on a basic pain scale, typically radiating up the affected limb. Puncture sites may bleed and often have associated redness and swelling. Pain may last up to 24 hours. Occasionally, foreign material may be left in the wound requiring removal. There also is a chance of secondary infection at the wound site, and severe envenomation can lead to local tissue necrosis.⁸ Systemic effects can occur in some cases, including nausea, vomiting, sweating, headache, dizziness, disorientation, palpitations, and even syncope.⁹ However, to our knowledge there are no documented cases of human death from a lionfish sting. Anaphylactic reactions are possible and require immediate treatment.⁶

A study conducted in the French West Indies evaluated 117 patients with lionfish envenomation and found that victims experienced severe pain and local edema (100%), paresthesia (90%), abdominal cramps (62%), extensive edema (53%), tachycardia (34%), skin rash (32%), gastrointestinal tract symptoms (28%), syncope (27%), transient weakness (24%), hypertension (21%), hypotension (18%), and hyperthermia (9%).⁹ Complications included local infection (18%) such as skin abscess (5%), skin necrosis (3%), and septic arthritis (2%). Twenty-two percent of patients were hospitalized and 8% required surgery. Local infectious complications were more frequent in those with multiple stings (19%). The study concluded that lionfish now represent a major health threat in the West Indies.⁹ As lionfish numbers have grown, health care providers are seeing increasing numbers of envenomation cases in areas of the coastal southeastern United States and Caribbean associated with considerable morbidity. Providers in nonendemic areas also may see envenomation injuries due to the lionfish popularity in home aquariums.⁹

Management

Individuals with lionfish stings should immerse the affected area in hot but not scalding water. Those with more serious injuries should seek medical attention. Home remedies that are generally contraindicated include application of topical papain or meat tenderizer.¹⁰ Data on ice packs are mixed, but because the toxin is heat labile, the most effective initial step in treatment is immersion of the affected area in water (temperature, 40°C to 45°C) for 30 to 90 minutes.⁶ The hot water inactivates the heat-labile toxin, leading to near-complete symptomatic relief in 80% of cases and moderate relief in an additional 14%. Immersion time more than 90 minutes considerably increases the risk for burns. Children should always be monitored to prevent burns. If a patient has received a nerve block for analgesia, the wound should not be immersed in hot water to avoid burns to the skin. The wound should be meticulously cleaned with saline irrigation, and radiography or ultrasonography should be performed as deemed necessary to look for any retained foreign bodies.⁸ Patients may require parenteral or oral analgesia as well as careful follow-up to ensure proper healing.⁹ Systemic symptoms require supportive care. Venomous fish wounds typically are small and superficial. Empiric antibiotic therapy is not advised for superficial wounds but may be required for clinically infected wounds.⁸ Tetanus prophylaxis should be given as appropriate to all affected patients. It has been noted that blister fluid contains high concentrations of lionfish venom, and when present, it increases the likelihood of converting the injury from a grade II to grade III wound with tissue necrosis; therefore, blisters should be drained or excised to decrease the chances of subsequent tissue necrosis.^11,12 If secondary infection such as cellulitis develops, antibiotics should be chosen to cover likely pathogens including common skin flora such as staphylococci and marine organisms such as Vibrio species. Wounds showing signs of infection should be cultured, with antibiotics adjusted according to sensitivities.⁵ Deeper wounds should be left open (unsutured) with a proper dressing to heal. Any wounds that involve vascular or joint structures require specialty management. Wounds involving joints may on occasion require surgical exploration and debridement.

Public Health Concerns

In an attempt to slow the growth of their population, human consumption of the fish has been encouraged. The lionfish toxin is inactivated by cooking, and the fish is considered a delicacy; however, a study in the Virgin Islands found that in areas with endemic ciguatera poisoning, 12% of lionfish carried amounts of the toxin above the level considered safe for consumption. This toxin is not inactivated by cooking or freezing and can lead to ciguatera fish poisoning for which there is no antidote and can be associated with prolonged neurotoxicity.¹³

Conclusion

As lionfish numbers continue to increase, physicians across multiple specialties and regions may see an increase in envenomation injuries. It is important that physicians are aware of how to recognize and treat lionfish stings, as prompt and comprehensive treatment provides benefit to the patient.

The lionfish (Pterois volitans) is a member of the Scorpaenidae family of venomous fish.^1-3 Lionfish are an invasive species originally from the Indian and Pacific oceans and the Red Sea that now are widely found throughout tropical and temperate oceans in both hemispheres. They are a popular aquarium fish and were inadvertently introduced in the Atlantic Ocean in South Florida during the late 1980s to early 1990s.^2,4 Since then, lionfish have spread into reef systems throughout the Atlantic Ocean, Caribbean Sea, and Gulf of Mexico in rapidly growing numbers, and they are now fo und all along the southeastern coast of the United States.⁵

Characteristics

Lionfish are brightly colored with red or maroon and white stripes, tentacles above the eyes and mouth, fan-shaped pectoral fins, and spines that deliver an especially painful venomous sting that often results in edema (Figure 1). They have 12 dorsal spines, 2 pelvic spines, and 3 anal spines.

Symptoms of Envenomation

As lionfish continue to spread to popular areas of the southeast Atlantic Ocean and Caribbean Sea, the chances of human contact with lionfish have increased. Lionfish stings are now the second most common marine envenomation injury after those caused by stingrays.⁴ Lionfish stings usually occur on the hands, fingers, or forearms during handling of the fish in ocean waters or in maintenance of aquariums. The mechanism of the venom apparatus is similar for all venomous fish. The spines have surrounding integumentary sheaths containing venom that rupture and inject venom when they penetrate the skin.⁶ The venom is a heat-labile neuromuscular toxin that causes edema (Figure 2), plasma extravasation, and thrombotic skin lesions.⁷

Wounds are classified into 3 categories: grade I consists of local erythema/ecchymosis, grade II involves vesicle or blister formation, and grade III denotes wounds that develop local necrosis.⁸ The sting causes immediate and severe throbbing pain, often described as excruciating or rated 10/10 on a basic pain scale, typically radiating up the affected limb. Puncture sites may bleed and often have associated redness and swelling. Pain may last up to 24 hours. Occasionally, foreign material may be left in the wound requiring removal. There also is a chance of secondary infection at the wound site, and severe envenomation can lead to local tissue necrosis.⁸ Systemic effects can occur in some cases, including nausea, vomiting, sweating, headache, dizziness, disorientation, palpitations, and even syncope.⁹ However, to our knowledge there are no documented cases of human death from a lionfish sting. Anaphylactic reactions are possible and require immediate treatment.⁶

A study conducted in the French West Indies evaluated 117 patients with lionfish envenomation and found that victims experienced severe pain and local edema (100%), paresthesia (90%), abdominal cramps (62%), extensive edema (53%), tachycardia (34%), skin rash (32%), gastrointestinal tract symptoms (28%), syncope (27%), transient weakness (24%), hypertension (21%), hypotension (18%), and hyperthermia (9%).⁹ Complications included local infection (18%) such as skin abscess (5%), skin necrosis (3%), and septic arthritis (2%). Twenty-two percent of patients were hospitalized and 8% required surgery. Local infectious complications were more frequent in those with multiple stings (19%). The study concluded that lionfish now represent a major health threat in the West Indies.⁹ As lionfish numbers have grown, health care providers are seeing increasing numbers of envenomation cases in areas of the coastal southeastern United States and Caribbean associated with considerable morbidity. Providers in nonendemic areas also may see envenomation injuries due to the lionfish popularity in home aquariums.⁹

Management

Individuals with lionfish stings should immerse the affected area in hot but not scalding water. Those with more serious injuries should seek medical attention. Home remedies that are generally contraindicated include application of topical papain or meat tenderizer.¹⁰ Data on ice packs are mixed, but because the toxin is heat labile, the most effective initial step in treatment is immersion of the affected area in water (temperature, 40°C to 45°C) for 30 to 90 minutes.⁶ The hot water inactivates the heat-labile toxin, leading to near-complete symptomatic relief in 80% of cases and moderate relief in an additional 14%. Immersion time more than 90 minutes considerably increases the risk for burns. Children should always be monitored to prevent burns. If a patient has received a nerve block for analgesia, the wound should not be immersed in hot water to avoid burns to the skin. The wound should be meticulously cleaned with saline irrigation, and radiography or ultrasonography should be performed as deemed necessary to look for any retained foreign bodies.⁸ Patients may require parenteral or oral analgesia as well as careful follow-up to ensure proper healing.⁹ Systemic symptoms require supportive care. Venomous fish wounds typically are small and superficial. Empiric antibiotic therapy is not advised for superficial wounds but may be required for clinically infected wounds.⁸ Tetanus prophylaxis should be given as appropriate to all affected patients. It has been noted that blister fluid contains high concentrations of lionfish venom, and when present, it increases the likelihood of converting the injury from a grade II to grade III wound with tissue necrosis; therefore, blisters should be drained or excised to decrease the chances of subsequent tissue necrosis.^11,12 If secondary infection such as cellulitis develops, antibiotics should be chosen to cover likely pathogens including common skin flora such as staphylococci and marine organisms such as Vibrio species. Wounds showing signs of infection should be cultured, with antibiotics adjusted according to sensitivities.⁵ Deeper wounds should be left open (unsutured) with a proper dressing to heal. Any wounds that involve vascular or joint structures require specialty management. Wounds involving joints may on occasion require surgical exploration and debridement.

Public Health Concerns

In an attempt to slow the growth of their population, human consumption of the fish has been encouraged. The lionfish toxin is inactivated by cooking, and the fish is considered a delicacy; however, a study in the Virgin Islands found that in areas with endemic ciguatera poisoning, 12% of lionfish carried amounts of the toxin above the level considered safe for consumption. This toxin is not inactivated by cooking or freezing and can lead to ciguatera fish poisoning for which there is no antidote and can be associated with prolonged neurotoxicity.¹³

Conclusion

As lionfish numbers continue to increase, physicians across multiple specialties and regions may see an increase in envenomation injuries. It is important that physicians are aware of how to recognize and treat lionfish stings, as prompt and comprehensive treatment provides benefit to the patient.

Clothes moths are common pests found inside buildings such as homes, stores, and museums. The most common species of importance include the webbing clothes moth (Tineola bisselliella)(Figure) and the casemaking clothes moth (Tineola pellionella). Both species target textiles such as wool, rugs, feathers, felts, hair, furs, and even grains.^1,2 They avoid synthetics and plant materials such as cottons.¹

Characteristics

Adult clothes moths extend 7 to 8 mm and are a golden (T bisselliella) to brown (T pellionella) color with fringed wings and a tuft on their heads.^1,3 Adults do not eat; females die within a few days of laying eggs, while males live approximately 1 month. Once laid, eggs hatch within 4 to 10 days.^1,3 The larvae (caterpillars) incur damage to clothes and other household goods. Fully mature larvae are 12- to 13-mm long, and the Tineola species have white- to cream-colored bodies with brown heads. The webbing clothes moth larva lacks ocelli (eyes), while the casemaking moth larva has a singular ocellus.¹

Transmission

An infestation is evidenced by woolen items that have furrows or holes in them. Pheromone traps also can expose an active infestation.³ The webbing moth larvae can be found beneath a self-spun silken mat on the food source that offers the insect protection and camouflage while it eats; the mat collects frass (feces) and clothes particles.^1,3,4 The casemaking moth larvae drag around a portable silken bag that takes on the color of the fabric being eaten and serves as a refuge when disturbed.^1,3,4 Both adult and larval stages prefer low light conditions. The total time of development from caterpillar to adult varies depending on the temperature and humidity of the environment, but most clothes moths complete their life cycle within 1 to 3 months.¹

Management of an Infestation

Multiple infestation treatment options exist should a patient present with a clothes moth infestation. Infested clothing articles or small blankets and rugs can be dry-cleaned or laundered. Any items not in use should be laundered before being sealed in airtight storage containers. Mothball vapor at appropriate concentrations is lethal to the moths, and when possible, clothing should be stored with mothballs or flakes at the concentration recommended by the manufacturer.⁴ Individuals should avoid application of household insecticides to clothing or bedding, which may be poisonous to people.^1,4 Freezing, heating, and dry ice fumigation techniques also can be used to treat infested products.³ Cedarwood usually is insufficient to deter an infestation, as the oil vapor rarely reaches an effective concentration to repel or harm the insects.^3,4 Strict housekeeping with attention to vacuuming carpets, baseboards, closets, and laundering all linens and furniture covers can further reduce an infestation.⁴ Clothes items can be set in the sunlight and brushed to help loosen the pests, as they dislike direct light and may fall from the garments.³ Dust insecticides also can be used per the manufacturer label to treat crevices and baseboards in an active area of infestation that may otherwise be difficult to clean.³ If an extensive infestation exists or larger items are infested, then a professional pest control agency should be employed for proper eradication.

Conclusion

Understanding the life cycle and basic biology of clothes moths and other common household pests will help the clinician identify an infestation and counsel patients if an insect is a true ectoparasite. Clothes moth larvae are not parasites but can be found on clothing and can be confused with myiasis or true parasites.

Clothes moths are common pests found inside buildings such as homes, stores, and museums. The most common species of importance include the webbing clothes moth (Tineola bisselliella)(Figure) and the casemaking clothes moth (Tineola pellionella). Both species target textiles such as wool, rugs, feathers, felts, hair, furs, and even grains.^1,2 They avoid synthetics and plant materials such as cottons.¹

Characteristics

Adult clothes moths extend 7 to 8 mm and are a golden (T bisselliella) to brown (T pellionella) color with fringed wings and a tuft on their heads.^1,3 Adults do not eat; females die within a few days of laying eggs, while males live approximately 1 month. Once laid, eggs hatch within 4 to 10 days.^1,3 The larvae (caterpillars) incur damage to clothes and other household goods. Fully mature larvae are 12- to 13-mm long, and the Tineola species have white- to cream-colored bodies with brown heads. The webbing clothes moth larva lacks ocelli (eyes), while the casemaking moth larva has a singular ocellus.¹

Transmission

An infestation is evidenced by woolen items that have furrows or holes in them. Pheromone traps also can expose an active infestation.³ The webbing moth larvae can be found beneath a self-spun silken mat on the food source that offers the insect protection and camouflage while it eats; the mat collects frass (feces) and clothes particles.^1,3,4 The casemaking moth larvae drag around a portable silken bag that takes on the color of the fabric being eaten and serves as a refuge when disturbed.^1,3,4 Both adult and larval stages prefer low light conditions. The total time of development from caterpillar to adult varies depending on the temperature and humidity of the environment, but most clothes moths complete their life cycle within 1 to 3 months.¹

Management of an Infestation

Multiple infestation treatment options exist should a patient present with a clothes moth infestation. Infested clothing articles or small blankets and rugs can be dry-cleaned or laundered. Any items not in use should be laundered before being sealed in airtight storage containers. Mothball vapor at appropriate concentrations is lethal to the moths, and when possible, clothing should be stored with mothballs or flakes at the concentration recommended by the manufacturer.⁴ Individuals should avoid application of household insecticides to clothing or bedding, which may be poisonous to people.^1,4 Freezing, heating, and dry ice fumigation techniques also can be used to treat infested products.³ Cedarwood usually is insufficient to deter an infestation, as the oil vapor rarely reaches an effective concentration to repel or harm the insects.^3,4 Strict housekeeping with attention to vacuuming carpets, baseboards, closets, and laundering all linens and furniture covers can further reduce an infestation.⁴ Clothes items can be set in the sunlight and brushed to help loosen the pests, as they dislike direct light and may fall from the garments.³ Dust insecticides also can be used per the manufacturer label to treat crevices and baseboards in an active area of infestation that may otherwise be difficult to clean.³ If an extensive infestation exists or larger items are infested, then a professional pest control agency should be employed for proper eradication.

Conclusion

Understanding the life cycle and basic biology of clothes moths and other common household pests will help the clinician identify an infestation and counsel patients if an insect is a true ectoparasite. Clothes moth larvae are not parasites but can be found on clothing and can be confused with myiasis or true parasites.

Clothes moths are common pests found inside buildings such as homes, stores, and museums. The most common species of importance include the webbing clothes moth (Tineola bisselliella)(Figure) and the casemaking clothes moth (Tineola pellionella). Both species target textiles such as wool, rugs, feathers, felts, hair, furs, and even grains.^1,2 They avoid synthetics and plant materials such as cottons.¹

Characteristics

Adult clothes moths extend 7 to 8 mm and are a golden (T bisselliella) to brown (T pellionella) color with fringed wings and a tuft on their heads.^1,3 Adults do not eat; females die within a few days of laying eggs, while males live approximately 1 month. Once laid, eggs hatch within 4 to 10 days.^1,3 The larvae (caterpillars) incur damage to clothes and other household goods. Fully mature larvae are 12- to 13-mm long, and the Tineola species have white- to cream-colored bodies with brown heads. The webbing clothes moth larva lacks ocelli (eyes), while the casemaking moth larva has a singular ocellus.¹

Transmission

An infestation is evidenced by woolen items that have furrows or holes in them. Pheromone traps also can expose an active infestation.³ The webbing moth larvae can be found beneath a self-spun silken mat on the food source that offers the insect protection and camouflage while it eats; the mat collects frass (feces) and clothes particles.^1,3,4 The casemaking moth larvae drag around a portable silken bag that takes on the color of the fabric being eaten and serves as a refuge when disturbed.^1,3,4 Both adult and larval stages prefer low light conditions. The total time of development from caterpillar to adult varies depending on the temperature and humidity of the environment, but most clothes moths complete their life cycle within 1 to 3 months.¹

Management of an Infestation

Multiple infestation treatment options exist should a patient present with a clothes moth infestation. Infested clothing articles or small blankets and rugs can be dry-cleaned or laundered. Any items not in use should be laundered before being sealed in airtight storage containers. Mothball vapor at appropriate concentrations is lethal to the moths, and when possible, clothing should be stored with mothballs or flakes at the concentration recommended by the manufacturer.⁴ Individuals should avoid application of household insecticides to clothing or bedding, which may be poisonous to people.^1,4 Freezing, heating, and dry ice fumigation techniques also can be used to treat infested products.³ Cedarwood usually is insufficient to deter an infestation, as the oil vapor rarely reaches an effective concentration to repel or harm the insects.^3,4 Strict housekeeping with attention to vacuuming carpets, baseboards, closets, and laundering all linens and furniture covers can further reduce an infestation.⁴ Clothes items can be set in the sunlight and brushed to help loosen the pests, as they dislike direct light and may fall from the garments.³ Dust insecticides also can be used per the manufacturer label to treat crevices and baseboards in an active area of infestation that may otherwise be difficult to clean.³ If an extensive infestation exists or larger items are infested, then a professional pest control agency should be employed for proper eradication.

Conclusion

Understanding the life cycle and basic biology of clothes moths and other common household pests will help the clinician identify an infestation and counsel patients if an insect is a true ectoparasite. Clothes moth larvae are not parasites but can be found on clothing and can be confused with myiasis or true parasites.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.