Environmental Dermatology

With the growing popularity of water sports and a proliferation of invasive species, human injuries from marine animal envenomation continue to rise.^1-3 Members of the scorpionfish family Scorpaenidae are second only to stingrays as the leading cause of the 40,000 to 50,000 injuries annually from marine life worldwide.⁴ Because scorpionfish represent a growing threat and competition with native species, it has been suggested that they could replace endangered species on restaurant menus.^5-8 Scorpionfish have been introduced by humans from tropical to temperate seas and are now common off the coast of California and the eastern coast from New York to Florida, as well as in the Caribbean, the Bahamas, and off the southern coast of Brazil. Victims of scorpionfish stings experience considerable pain and may require days to weeks to fully recover, highlighting the socioeconomic costs and burden of scorpionfish envenomation.^9,10 Fishers, divers, swimmers, and aquarium owners are most often affected.

Family

The common term scorpionfish refers to both the family Scorpaenidae and the genus Scorpaena. Members of this family possess similar dorsal, anal, and pelvic fins, though they vary between genera in their size and the potency of the venom they insulate. Other familiar members include the genus Pterois (lionfish) and Synanceja (stonefish). Synanceja are the most venomous within the group, but scorpionfish stings more commonly arise from Pterois and Scorpaena.⁸ Because of the rare shapes and vibrant colors of scorpionfish, some traders and aquarium owners will seek and pay high prices for these fish, providing further opportunity for envenomation.^11,12

Characteristics

Scorpionfish have with a high variation in color, ranging from lighter grays to intense reds depending on their geographic location and habitat. Synanceja are bland in coloration, blending in with rocks and gravel, but the more dramatic-appearing Scorpaena exhibit a large cranium and wide range of multicolored patterns (Figure 1).¹³Pterois serve as the most conspicuous member of the group with brightly colored red and white stripes (Figure 2). Scorpionfish commonly grow up to 19 inches long and boast 12 dorsal, 2 pelvic, and 3 anal spines housing 5 to 10 mg of venom.¹⁴ An integumentary sheath encapsulates each spine housing the glandular tissue that produces the potent venom.

Photograph courtesy of Sylvain Le Bris (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Toxin Properties

Unlike Pterois and Synanceja, Scorpaena do not have venom ducts around their glands, complicating the work of marine biologists aiming to extract and study the venomous toxins. Several studies have managed to isolate scorpionfish venom and overcome its unstable heat-labile nature to investigate its biologic properties.^15-20 Several high-molecular-weight proteins (50–800 kDa) comprise the venom, including hyaluronidase, integrin-inhibiting factors, capillary permeability factor, proteases, and some less-understood cytolytic toxins. These factors provoke the inflammatory, proteolytic, hemorrhagic, cardiovascular, and hemolytic biologic activities at both the local and systemic levels, directing damage to wounded tissues and inducing vascular and tissue permeability to reach cellular processes far and wide. Mediators of inflammation include tumor necrosis factor, IL-6, and monocyte chemoattractant protein 1, followed by neutrophils and other mononuclear cells, initiating the immune response at the wound site. Toxin potency remains for up to 2 days after fish death.¹

Photograph courtesy of 808_Diver (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Clinical Manifestation

Physicians may be guided by clinical symptoms in identifying scorpionfish stings, as the patient may not know the identity of their marine assailant. Initially, individuals punctured by scorpionfish spikes will experience an acute pain and burning sensation at the puncture site that may be accompanied by systemic symptoms such as nausea, vomiting, diarrhea, tachycardia, hypotension, loss of consciousness, difficulty breathing, and delirium.^9,21-23 The pain will intensify and radiate distal to the site of envenomation, and the wound may exhibit vesiculation, erythema, bruising, pallor, and notable edema.^4,24 Pain intensity peaks at 30 to 90 minutes after envenomation, and other systemic symptoms generally last for 24 to 48 hours.²⁵ If patients do not seek prompt treatment, secondary infection may ensue, and the lingering venom in the blister may cause dermal necrosis, paresthesia, and anesthesia. Chronic sequelae may include joint contractures, compartment syndrome, necrotic ulcers, and chronic neuropathy.¹

Management

Treatment of scorpionfish stings primarily is palliative and aimed at symptom reduction. Patients should immediately treat wounds with hot but not scalding water immersion.^26,27 Given the thermolabile components of scorpionfish venom, the most effective treatment is to soak the affected limb in water 42 °C to 45 °C for 30 to 90 minutes. Any higher temperature may pose risk for scalding burns. Children should be monitored throughout treatment.²⁸ If hot water immersion does not provide relief, oral analgesics may be considered. Stonefish antivenom is available and may be used for any scorpionfish sting given the shared biologic properties between genera. Providers evaluating stings could use sterile irrigation to clean wounds and search for foreign bodies including spine fragments; probing should be accomplished by instruments rather than a gloved finger. Providers should consider culturing wounds and prescribing antibiotics for suspected secondary infections. A tetanus toxoid history also should be elicited, and patients may have a booster administered, as indicated.²⁹

With the growing popularity of water sports and a proliferation of invasive species, human injuries from marine animal envenomation continue to rise.^1-3 Members of the scorpionfish family Scorpaenidae are second only to stingrays as the leading cause of the 40,000 to 50,000 injuries annually from marine life worldwide.⁴ Because scorpionfish represent a growing threat and competition with native species, it has been suggested that they could replace endangered species on restaurant menus.^5-8 Scorpionfish have been introduced by humans from tropical to temperate seas and are now common off the coast of California and the eastern coast from New York to Florida, as well as in the Caribbean, the Bahamas, and off the southern coast of Brazil. Victims of scorpionfish stings experience considerable pain and may require days to weeks to fully recover, highlighting the socioeconomic costs and burden of scorpionfish envenomation.^9,10 Fishers, divers, swimmers, and aquarium owners are most often affected.

Family

The common term scorpionfish refers to both the family Scorpaenidae and the genus Scorpaena. Members of this family possess similar dorsal, anal, and pelvic fins, though they vary between genera in their size and the potency of the venom they insulate. Other familiar members include the genus Pterois (lionfish) and Synanceja (stonefish). Synanceja are the most venomous within the group, but scorpionfish stings more commonly arise from Pterois and Scorpaena.⁸ Because of the rare shapes and vibrant colors of scorpionfish, some traders and aquarium owners will seek and pay high prices for these fish, providing further opportunity for envenomation.^11,12

Characteristics

Scorpionfish have with a high variation in color, ranging from lighter grays to intense reds depending on their geographic location and habitat. Synanceja are bland in coloration, blending in with rocks and gravel, but the more dramatic-appearing Scorpaena exhibit a large cranium and wide range of multicolored patterns (Figure 1).¹³Pterois serve as the most conspicuous member of the group with brightly colored red and white stripes (Figure 2). Scorpionfish commonly grow up to 19 inches long and boast 12 dorsal, 2 pelvic, and 3 anal spines housing 5 to 10 mg of venom.¹⁴ An integumentary sheath encapsulates each spine housing the glandular tissue that produces the potent venom.

Photograph courtesy of Sylvain Le Bris (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Toxin Properties

Unlike Pterois and Synanceja, Scorpaena do not have venom ducts around their glands, complicating the work of marine biologists aiming to extract and study the venomous toxins. Several studies have managed to isolate scorpionfish venom and overcome its unstable heat-labile nature to investigate its biologic properties.^15-20 Several high-molecular-weight proteins (50–800 kDa) comprise the venom, including hyaluronidase, integrin-inhibiting factors, capillary permeability factor, proteases, and some less-understood cytolytic toxins. These factors provoke the inflammatory, proteolytic, hemorrhagic, cardiovascular, and hemolytic biologic activities at both the local and systemic levels, directing damage to wounded tissues and inducing vascular and tissue permeability to reach cellular processes far and wide. Mediators of inflammation include tumor necrosis factor, IL-6, and monocyte chemoattractant protein 1, followed by neutrophils and other mononuclear cells, initiating the immune response at the wound site. Toxin potency remains for up to 2 days after fish death.¹

Photograph courtesy of 808_Diver (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Clinical Manifestation

Physicians may be guided by clinical symptoms in identifying scorpionfish stings, as the patient may not know the identity of their marine assailant. Initially, individuals punctured by scorpionfish spikes will experience an acute pain and burning sensation at the puncture site that may be accompanied by systemic symptoms such as nausea, vomiting, diarrhea, tachycardia, hypotension, loss of consciousness, difficulty breathing, and delirium.^9,21-23 The pain will intensify and radiate distal to the site of envenomation, and the wound may exhibit vesiculation, erythema, bruising, pallor, and notable edema.^4,24 Pain intensity peaks at 30 to 90 minutes after envenomation, and other systemic symptoms generally last for 24 to 48 hours.²⁵ If patients do not seek prompt treatment, secondary infection may ensue, and the lingering venom in the blister may cause dermal necrosis, paresthesia, and anesthesia. Chronic sequelae may include joint contractures, compartment syndrome, necrotic ulcers, and chronic neuropathy.¹

Management

Treatment of scorpionfish stings primarily is palliative and aimed at symptom reduction. Patients should immediately treat wounds with hot but not scalding water immersion.^26,27 Given the thermolabile components of scorpionfish venom, the most effective treatment is to soak the affected limb in water 42 °C to 45 °C for 30 to 90 minutes. Any higher temperature may pose risk for scalding burns. Children should be monitored throughout treatment.²⁸ If hot water immersion does not provide relief, oral analgesics may be considered. Stonefish antivenom is available and may be used for any scorpionfish sting given the shared biologic properties between genera. Providers evaluating stings could use sterile irrigation to clean wounds and search for foreign bodies including spine fragments; probing should be accomplished by instruments rather than a gloved finger. Providers should consider culturing wounds and prescribing antibiotics for suspected secondary infections. A tetanus toxoid history also should be elicited, and patients may have a booster administered, as indicated.²⁹

With the growing popularity of water sports and a proliferation of invasive species, human injuries from marine animal envenomation continue to rise.^1-3 Members of the scorpionfish family Scorpaenidae are second only to stingrays as the leading cause of the 40,000 to 50,000 injuries annually from marine life worldwide.⁴ Because scorpionfish represent a growing threat and competition with native species, it has been suggested that they could replace endangered species on restaurant menus.^5-8 Scorpionfish have been introduced by humans from tropical to temperate seas and are now common off the coast of California and the eastern coast from New York to Florida, as well as in the Caribbean, the Bahamas, and off the southern coast of Brazil. Victims of scorpionfish stings experience considerable pain and may require days to weeks to fully recover, highlighting the socioeconomic costs and burden of scorpionfish envenomation.^9,10 Fishers, divers, swimmers, and aquarium owners are most often affected.

Family

The common term scorpionfish refers to both the family Scorpaenidae and the genus Scorpaena. Members of this family possess similar dorsal, anal, and pelvic fins, though they vary between genera in their size and the potency of the venom they insulate. Other familiar members include the genus Pterois (lionfish) and Synanceja (stonefish). Synanceja are the most venomous within the group, but scorpionfish stings more commonly arise from Pterois and Scorpaena.⁸ Because of the rare shapes and vibrant colors of scorpionfish, some traders and aquarium owners will seek and pay high prices for these fish, providing further opportunity for envenomation.^11,12

Characteristics

Scorpionfish have with a high variation in color, ranging from lighter grays to intense reds depending on their geographic location and habitat. Synanceja are bland in coloration, blending in with rocks and gravel, but the more dramatic-appearing Scorpaena exhibit a large cranium and wide range of multicolored patterns (Figure 1).¹³Pterois serve as the most conspicuous member of the group with brightly colored red and white stripes (Figure 2). Scorpionfish commonly grow up to 19 inches long and boast 12 dorsal, 2 pelvic, and 3 anal spines housing 5 to 10 mg of venom.¹⁴ An integumentary sheath encapsulates each spine housing the glandular tissue that produces the potent venom.

Photograph courtesy of Sylvain Le Bris (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Toxin Properties

Unlike Pterois and Synanceja, Scorpaena do not have venom ducts around their glands, complicating the work of marine biologists aiming to extract and study the venomous toxins. Several studies have managed to isolate scorpionfish venom and overcome its unstable heat-labile nature to investigate its biologic properties.^15-20 Several high-molecular-weight proteins (50–800 kDa) comprise the venom, including hyaluronidase, integrin-inhibiting factors, capillary permeability factor, proteases, and some less-understood cytolytic toxins. These factors provoke the inflammatory, proteolytic, hemorrhagic, cardiovascular, and hemolytic biologic activities at both the local and systemic levels, directing damage to wounded tissues and inducing vascular and tissue permeability to reach cellular processes far and wide. Mediators of inflammation include tumor necrosis factor, IL-6, and monocyte chemoattractant protein 1, followed by neutrophils and other mononuclear cells, initiating the immune response at the wound site. Toxin potency remains for up to 2 days after fish death.¹

Photograph courtesy of 808_Diver (https://www.inaturalist.org/). Republished under the Creative Commons Attribution (CC BY-NC 4.0).

Clinical Manifestation

Physicians may be guided by clinical symptoms in identifying scorpionfish stings, as the patient may not know the identity of their marine assailant. Initially, individuals punctured by scorpionfish spikes will experience an acute pain and burning sensation at the puncture site that may be accompanied by systemic symptoms such as nausea, vomiting, diarrhea, tachycardia, hypotension, loss of consciousness, difficulty breathing, and delirium.^9,21-23 The pain will intensify and radiate distal to the site of envenomation, and the wound may exhibit vesiculation, erythema, bruising, pallor, and notable edema.^4,24 Pain intensity peaks at 30 to 90 minutes after envenomation, and other systemic symptoms generally last for 24 to 48 hours.²⁵ If patients do not seek prompt treatment, secondary infection may ensue, and the lingering venom in the blister may cause dermal necrosis, paresthesia, and anesthesia. Chronic sequelae may include joint contractures, compartment syndrome, necrotic ulcers, and chronic neuropathy.¹

Management

Treatment of scorpionfish stings primarily is palliative and aimed at symptom reduction. Patients should immediately treat wounds with hot but not scalding water immersion.^26,27 Given the thermolabile components of scorpionfish venom, the most effective treatment is to soak the affected limb in water 42 °C to 45 °C for 30 to 90 minutes. Any higher temperature may pose risk for scalding burns. Children should be monitored throughout treatment.²⁸ If hot water immersion does not provide relief, oral analgesics may be considered. Stonefish antivenom is available and may be used for any scorpionfish sting given the shared biologic properties between genera. Providers evaluating stings could use sterile irrigation to clean wounds and search for foreign bodies including spine fragments; probing should be accomplished by instruments rather than a gloved finger. Providers should consider culturing wounds and prescribing antibiotics for suspected secondary infections. A tetanus toxoid history also should be elicited, and patients may have a booster administered, as indicated.²⁹

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.

Traditional Uses

For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.^1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.⁴ Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.⁵

All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.⁶ Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.

Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.

Bioactivity

Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.^1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.^1,10

Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.¹¹ In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).¹ In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.⁵ All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.

Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.^7,12,13

Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).¹⁴ Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.

Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.^1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.¹⁶

The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.¹⁷ It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.¹⁶ Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.¹⁸

Safety, Toxicity, and Risks

Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.¹⁹ The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.²⁰

Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.⁴

Final Thoughts

The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.

Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.

Traditional Uses

For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.^1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.⁴ Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.⁵

All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.⁶ Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.

Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.

Bioactivity

Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.^1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.^1,10

Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.¹¹ In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).¹ In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.⁵ All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.

Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.^7,12,13

Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).¹⁴ Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.

Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.^1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.¹⁶

The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.¹⁷ It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.¹⁶ Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.¹⁸

Safety, Toxicity, and Risks

Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.¹⁹ The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.²⁰

Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.⁴

Final Thoughts

The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.

Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.

Traditional Uses

For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.^1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.⁴ Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.⁵

All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.⁶ Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.

Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.

Bioactivity

Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.^1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.^1,10

Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.¹¹ In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).¹ In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.⁵ All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.

Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.^7,12,13

Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).¹⁴ Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.

Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.^1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.¹⁶

The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.¹⁷ It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.¹⁶ Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.¹⁸

Safety, Toxicity, and Risks

Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.¹⁹ The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.²⁰

Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.⁴

Final Thoughts

The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Fleas (order Siphonaptera) are vectors for various diseases, such as plague (as carriers of Yersinia pestis) and rickettsial infections.^1-4 The sticktight flea (Echidnophaga gallinacea) commonly is seen on birds and mammals, including ground squirrels, dogs, cats, and rodents, and can attach to its host for days at a time by burrowing its head into the skin. Similar to other fleas, the sticktight flea needs a blood supply to reproduce.⁵ Therefore, it is important to study the sticktight flea, its habitat, and infection patterns to improve public health and prevent infestation.

Identification

Echidnophaga gallinacea is named for the female flea’s behavior—it “sticks tight” to the surface of the host by embedding its head into the skin for days at a time.⁵ The sticktight flea and the rat flea (Xenopsylla cheopis) can be differentiated by the sticktight’s reduced thorax and lack of a pleural rod (the vertical ridge that divides the mesosternum above the second pair of legs)(Figure, A and B). The sticktight flea can be differentiated from the dog flea (Ctenocephalides canis) and the cat flea (Ctenocephalides felis) by its lack of genal ctenidia (horizontal combs in the mustache area) and pronotal ctenidia (vertical combs behind the head)(Figure, B and C).^6,7 Other defining features of E gallinacea include 2 pairs of large postantennal setae (hairs) on its anteriorly flattened head; a C-shaped reproductive organ known as the spermatheca; and broad maxillary lacinia (Figure, C).⁸

Habitat, Seasonality, and Behavior

Echidnophaga gallinacea commonly infests the comb, wattles, and surrounding ears of chickens; the flea also has been found on dogs, cats, rodents, and other species of birds.⁹ The sticktight flea is more prevalent in summer and autumn, which may explain its predominance in warmer climates, including California, Florida, Mexico, Egypt, Africa, and Iran.^1,9-11

When a female sticktight flea begins to feed, it stays on the host for days at a time, waiting for a male.⁵ The female deposits its fertilized eggs in nests on the host or in lesions caused by infestation. Eventually, eggs hatch and fall into soil, where they lay dormant or grow to adulthood.⁵

Cutaneous Reaction to Infestation

Flea bites cause a hypersensitivity reaction, with pruritic pustules and erythematous papules that have a central punctum.¹² In a reported case in Los Angeles, California, a female sticktight flea buried itself into the cheek of a young boy for more than 12 hours. The lesion was not marked by surrounding erythema, tenderness, pruritus, or swelling; however, several days after the flea was removed, erythema developed at the site then spontaneously resolved.⁷ In a study of dogs that were infested with E gallinacea, the flea never disengaged to attach to a human; when the flea was deliberately placed on a human, it fed and left hastily.¹¹

Management

Because E gallinacea burrows its head into the skin, the best removal method is applying slow gentle traction under sterile conditions to ensure removal of mouthparts.⁷ An oral antihistamine can be administered or a topical antihistamine or corticosteroid can be applied to the affected area.¹² Flea infestation should be treated with an insecticide. Affected animals should be treated by a veterinarian using a pesticide, such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, or pyriproxyfen.¹³

Fleas (order Siphonaptera) are vectors for various diseases, such as plague (as carriers of Yersinia pestis) and rickettsial infections.^1-4 The sticktight flea (Echidnophaga gallinacea) commonly is seen on birds and mammals, including ground squirrels, dogs, cats, and rodents, and can attach to its host for days at a time by burrowing its head into the skin. Similar to other fleas, the sticktight flea needs a blood supply to reproduce.⁵ Therefore, it is important to study the sticktight flea, its habitat, and infection patterns to improve public health and prevent infestation.

Identification

Echidnophaga gallinacea is named for the female flea’s behavior—it “sticks tight” to the surface of the host by embedding its head into the skin for days at a time.⁵ The sticktight flea and the rat flea (Xenopsylla cheopis) can be differentiated by the sticktight’s reduced thorax and lack of a pleural rod (the vertical ridge that divides the mesosternum above the second pair of legs)(Figure, A and B). The sticktight flea can be differentiated from the dog flea (Ctenocephalides canis) and the cat flea (Ctenocephalides felis) by its lack of genal ctenidia (horizontal combs in the mustache area) and pronotal ctenidia (vertical combs behind the head)(Figure, B and C).^6,7 Other defining features of E gallinacea include 2 pairs of large postantennal setae (hairs) on its anteriorly flattened head; a C-shaped reproductive organ known as the spermatheca; and broad maxillary lacinia (Figure, C).⁸

Habitat, Seasonality, and Behavior

Echidnophaga gallinacea commonly infests the comb, wattles, and surrounding ears of chickens; the flea also has been found on dogs, cats, rodents, and other species of birds.⁹ The sticktight flea is more prevalent in summer and autumn, which may explain its predominance in warmer climates, including California, Florida, Mexico, Egypt, Africa, and Iran.^1,9-11

When a female sticktight flea begins to feed, it stays on the host for days at a time, waiting for a male.⁵ The female deposits its fertilized eggs in nests on the host or in lesions caused by infestation. Eventually, eggs hatch and fall into soil, where they lay dormant or grow to adulthood.⁵

Cutaneous Reaction to Infestation

Flea bites cause a hypersensitivity reaction, with pruritic pustules and erythematous papules that have a central punctum.¹² In a reported case in Los Angeles, California, a female sticktight flea buried itself into the cheek of a young boy for more than 12 hours. The lesion was not marked by surrounding erythema, tenderness, pruritus, or swelling; however, several days after the flea was removed, erythema developed at the site then spontaneously resolved.⁷ In a study of dogs that were infested with E gallinacea, the flea never disengaged to attach to a human; when the flea was deliberately placed on a human, it fed and left hastily.¹¹

Management

Because E gallinacea burrows its head into the skin, the best removal method is applying slow gentle traction under sterile conditions to ensure removal of mouthparts.⁷ An oral antihistamine can be administered or a topical antihistamine or corticosteroid can be applied to the affected area.¹² Flea infestation should be treated with an insecticide. Affected animals should be treated by a veterinarian using a pesticide, such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, or pyriproxyfen.¹³

Fleas (order Siphonaptera) are vectors for various diseases, such as plague (as carriers of Yersinia pestis) and rickettsial infections.^1-4 The sticktight flea (Echidnophaga gallinacea) commonly is seen on birds and mammals, including ground squirrels, dogs, cats, and rodents, and can attach to its host for days at a time by burrowing its head into the skin. Similar to other fleas, the sticktight flea needs a blood supply to reproduce.⁵ Therefore, it is important to study the sticktight flea, its habitat, and infection patterns to improve public health and prevent infestation.

Identification

Echidnophaga gallinacea is named for the female flea’s behavior—it “sticks tight” to the surface of the host by embedding its head into the skin for days at a time.⁵ The sticktight flea and the rat flea (Xenopsylla cheopis) can be differentiated by the sticktight’s reduced thorax and lack of a pleural rod (the vertical ridge that divides the mesosternum above the second pair of legs)(Figure, A and B). The sticktight flea can be differentiated from the dog flea (Ctenocephalides canis) and the cat flea (Ctenocephalides felis) by its lack of genal ctenidia (horizontal combs in the mustache area) and pronotal ctenidia (vertical combs behind the head)(Figure, B and C).^6,7 Other defining features of E gallinacea include 2 pairs of large postantennal setae (hairs) on its anteriorly flattened head; a C-shaped reproductive organ known as the spermatheca; and broad maxillary lacinia (Figure, C).⁸

Habitat, Seasonality, and Behavior

Echidnophaga gallinacea commonly infests the comb, wattles, and surrounding ears of chickens; the flea also has been found on dogs, cats, rodents, and other species of birds.⁹ The sticktight flea is more prevalent in summer and autumn, which may explain its predominance in warmer climates, including California, Florida, Mexico, Egypt, Africa, and Iran.^1,9-11

When a female sticktight flea begins to feed, it stays on the host for days at a time, waiting for a male.⁵ The female deposits its fertilized eggs in nests on the host or in lesions caused by infestation. Eventually, eggs hatch and fall into soil, where they lay dormant or grow to adulthood.⁵

Cutaneous Reaction to Infestation

Flea bites cause a hypersensitivity reaction, with pruritic pustules and erythematous papules that have a central punctum.¹² In a reported case in Los Angeles, California, a female sticktight flea buried itself into the cheek of a young boy for more than 12 hours. The lesion was not marked by surrounding erythema, tenderness, pruritus, or swelling; however, several days after the flea was removed, erythema developed at the site then spontaneously resolved.⁷ In a study of dogs that were infested with E gallinacea, the flea never disengaged to attach to a human; when the flea was deliberately placed on a human, it fed and left hastily.¹¹

Management

Because E gallinacea burrows its head into the skin, the best removal method is applying slow gentle traction under sterile conditions to ensure removal of mouthparts.⁷ An oral antihistamine can be administered or a topical antihistamine or corticosteroid can be applied to the affected area.¹² Flea infestation should be treated with an insecticide. Affected animals should be treated by a veterinarian using a pesticide, such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, or pyriproxyfen.¹³

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.<sup>6</sup>

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).<i>1</i>

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.<sup>6</sup>

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).<i>1</i>

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.<sup>6</sup>

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).<i>1</i>

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

The genus Leishmania comprises protozoan parasites that cause approximately 2 million new cases of leishmaniasis each year across 98 countries.¹ These protozoa are obligate intracellular parasites of phlebotomine sandfly species that transmit leishmaniasis and result in a considerable parasitic cause of fatalities globally, second only to malaria.^2,3

Phlebotomine sandflies primarily live in tropical and subtropical regions and function as vectors for many pathogens in addition to Leishmania species, such as Bartonella species and arboviruses.³ In 2004, it was noted that the majority of leishmaniasis cases affected developing countries: 90% of visceral leishmaniasis cases occurred in Bangladesh, India, Nepal, Sudan, and Brazil, and 90% of cutaneous leishmaniasis cases occurred in Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia, and Syria.⁴ Of note, with recent environmental changes, phlebotomine sandflies have gradually migrated to more northerly latitudes, extending into Europe.⁵

Twenty Leishmania species and 30 sandfly species have been identified as causes of leishmaniasis.⁴Leishmania infection occurs when an infected sandfly bites a mammalian host and transmits the parasite’s flagellated form, known as a promastigote. Host inflammatory cells, such as monocytes and dendritic cells, phagocytize parasites that enter the skin. The interaction between parasites and dendritic cells become an important factor in the outcome of Leishmania infection in the host because dendritic cells promote development of CD4 and CD8 T lymphocytes with specificity to target Leishmania parasites and protect the host.¹

The number of cases of leishmaniasis has increased worldwide, most likely due to changes in the environment and human behaviors such as urbanization, the creation of new settlements, and migration from rural to urban areas.^3,5 Important risk factors in individual patients include malnutrition; low-quality housing and sanitation; a history of migration or travel; and immunosuppression, such as that caused by HIV co-infection.^2,5

Case Report

An otherwise healthy 25-year-old Bangladeshi man presented to our community hospital for evaluation of a painful leg ulcer of 1 month’s duration. The patient had migrated from Bangladesh to Panama, then to Costa Rica, followed by Guatemala, Honduras, Mexico, and, last, Texas. In Texas, he was identified by the US Immigration and Customs Enforcement, transported to a detention facility, and transferred to this hospital shortly afterward.

The patient reported that, during his extensive migration, he had lived in the jungle and reported what he described as mosquito bites on the legs. He subsequently developed a 3-cm ulcerated and crusted plaque with rolled borders on the right medial ankle (Figure 1). In addition, he had a palpable nodular cord on the medial leg from the ankle lesion to the mid thigh that was consistent with lymphocutaneous spread. Ultrasonography was negative for deep-vein thrombosis.

Because the patient’s recent migration from Central America was highly concerning for microbial infection, vancomycin and piperacillin-tazobactam were started empirically on admission. A punch biopsy from the right medial ankle was nondiagnostic, showing acute and chronic necrotizing inflammation along with numerous epithelioid histiocytes with a vaguely granulomatous appearance (Figure 2). A specimen from the right medial ankle that had already been taken by an astute border patrol medical provider was sent to the Centers for Disease Control and Prevention (CDC) for polymerase chain reaction analysis following admission and was found to be positive for Leishmania panamensis.

Given the concern for mucocutaneous leishmaniasis with this particular species, otolaryngology was consulted; however, the patient did not demonstrate mucocutaneous disease. Because of the elevated risk for persistent disease with L panamensis, systemic therapy was indicated and administered: IV amphotericin B 200 mg on days 1 through 5 and again on day 10. Improvement in the ulcer was seen after the 10-day regimen was completed.

Comment

Leishmaniasis can be broadly classified by geographic region or clinical presentation. Under the geographic region system, leishmaniasis can be categorized as Old World or New World. Old World leishmaniasis primarily is transmitted by Phlebotomus sandflies and carries the parasites Leishmania major and Leishmania tropica, among others. New World leishmaniasis is caused by Lutzomyia sandflies, which carry Leishmania mexicana, Leishmania braziliensis, Leishmania amazonensis, and others.⁶

Our patient presented with cutaneous leishmaniasis, one of 4 primary clinical disease forms of leishmaniasis; the other 3 forms under this classification system are diffuse cutaneous, mucocutaneous, and visceral leishmaniasis, also known as kala-azar.^3,6 Cutaneous leishmaniasis is limited to the skin, particularly the face and extremities. This form is more common with Old World vectors, with most cases occurring in Peru, Brazil, and the Middle East. In Old World cutaneous leishmaniasis, the disease begins with a solitary nodule at the site of the bite that ulcerates and can continue to spread in a sporotrichoid pattern. This cutaneous form tends to heal slowly over months to years with residual scarring. New World cutaneous leishmaniasis can present with a variety of clinical manifestations, including ulcerative, sarcoidlike, miliary, and nodular lesions.^6,7

The diffuse form of cutaneous leishmaniasis begins in a similar manner to the Old World cutaneous form: a single nodule spreads widely over the body, especially the nose, and covers the patient’s skin with keloidal or verrucous lesions that do not ulcerate. These nodules contain large groupings of Leishmania-filled foamy macrophages. Often, patients with diffuse cutaneous leishmaniasis are immunosuppressed and are unable to develop an immune response to leishmanin and other skin antigens.^6,7

Mucocutaneous leishmaniasis predominantly is caused by the New World species L braziliensis but also has been attributed to L amazonensis, L panamensis, and L guyanensis. This form manifests as mucosal lesions that can develop simultaneously with cutaneous lesions but more commonly appear months to years after resolution of the skin infection. Patients often present with ulceration of the lip, nose, and oropharynx, and destruction of the nasopharynx can result in severe consequences such as obstruction of the airway and perforation of the nasal septum (also known as espundia).^6,7

The most severe presentation of leishmaniasis is the visceral form (kala-azar), which presents with parasitic infection of the liver, spleen, and bone marrow. Most commonly caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi, this form has a long incubation period spanning months to years before presenting with diarrhea, hepatomegaly, splenomegaly, darkening of the skin (in Hindi, kala-azar means “black fever”), pancytopenia, lymphadenopathy, nephritis, and intestinal hemorrhage, among other severe manifestations. Visceral leishmaniasis has a poor prognosis: patients succumb to disease within 2 years if not treated.^6,7

Diagnosis—Diagnosing leishmaniasis starts with a complete personal and medical history, paying close attention to travel and exposures. Diagnosis is most successfully performed by polymerase chain reaction analysis, which is both highly sensitive and specific but also can be determined by culture using Novy-McNeal-Nicolle medium or by light microscopy. Histologic findings include the marquee sign, which describes an array of amastigotes (promastigotes that have developed into the intracellular tissue-stage form) with kinetoplasts surrounding the periphery of parasitized histiocytes. Giemsa staining can be helpful in identifying organisms.^2,6,7

The diagnosis in our case was challenging, as none of the above findings were seen in our patient. The specimen taken by the border patrol medical provider was negative on Gram, Giemsa, and Grocott-Gömöri methenamine silver staining; no amastigotes were identified. Another diagnostic modality (not performed in our patient) is the Montenegro delayed skin-reaction test, which often is positive in patients with cutaneous leishmaniasis but also yields a positive result in patients who have been cured of Leishmania infection.⁶

An important consideration in the diagnostic workup of leishmaniasis is that collaboration with the CDC can be helpful, such as in our case, as they provide clear guidance for specimen collection and processing.²

Treatment—Treating leishmaniasis is challenging and complex. Even the initial decision to treat depends on several factors, including the form of infection. Most visceral and mucocutaneous infections should be treated due to both the lack of self-resolution of these forms and the higher risk for a potentially life-threatening disease course; in contrast, cutaneous forms require further consideration before initiating treatment. Some indicators for treating cutaneous leishmaniasis include widespread infection, intention to decrease scarring, and lesions with the potential to cause further complications (eg, on the face or ears or close to joints).^6-8

The treatment of choice for cutaneous and mucocutaneous leishmaniasis is pentavalent antimony; however, this drug can only be obtained in the United States for investigational use, requiring approval by the CDC. A 20-day intravenous or intramuscular course of 20 mg/kg per day typically is used for cutaneous cases; a 28-day course typically is used for mucosal forms.

Amphotericin B is not only the treatment of choice for visceral leishmaniasis but also is an important alternative therapy for patients with mucosal leishmaniasis or who are co-infected with HIV. Patients with visceral infection also should receive supportive care for any concomitant afflictions, such as malnutrition or other infections. Although different regimens have been described, the US Food and Drug Administration has created outlines of specific intravenous infusion schedules for liposomal amphotericin B in immunocompetent and immunosuppressed patients.⁸ Liposomal amphotericin B also has a more favorable toxicity profile than conventional amphotericin B deoxycholate, which is otherwise effective in combating visceral leishmaniasis.^6-8

Other treatments that have been attempted include pentamidine, miltefosine, thermotherapy, oral itraconazole and fluconazole, rifampicin, metronidazole and cotrimoxazole, dapsone, photodynamic therapy, thermotherapy, topical paromomycin formulations, intralesional pentavalent antimony, and laser cryotherapy. Notable among these other agents is miltefosine, a US Food and Drug Administration–approved oral medication for adults and adolescents (used off-label for patients younger than 12 years) with cutaneous leishmaniasis caused by L braziliensis, L panamensis, or L guyanensis. Other oral options mentioned include the so-called azole antifungal medications, which historically have produced variable results. From the CDC’s reports, ketoconazole was moderately effective in Guatemala and Panama,⁸ whereas itraconazole did not demonstrate efficacy in Colombia, and the efficacy of fluconazole was inconsistent in different countries.⁸ When considering one of the local (as opposed to oral and parenteral) therapies mentioned, the extent of cutaneous findings as well as the risk of mucosal spread should be factored in.^6-8

Understandably, a number of considerations can come into play in determining the appropriate treatment modality, including body region affected, clinical form, severity, and Leishmania species.^6-8 Our case is of particular interest because it demonstrates the complexities behind the diagnosis and treatment of cutaneous leishmaniasis, with careful consideration geared toward the species; for example, because our patient was infected with L panamensis, which is known to cause mucocutaneous disease, the infectious disease service decided to pursue systemic therapy with amphotericin B rather than topical treatment.

Prevention—Vector control is the primary means of preventing leishmaniasis under 2 umbrellas: environmental management and synthetic insecticides. The goal of environmental management is to eliminate the phlebotomine sandfly habitat; this was the primary method of vector control until 1940. Until that time, tree stumps were removed, indoor cracks and crevices were filled to prevent sandfly emergence, and areas around animal shelters were cleaned. These methods were highly dependent on community awareness and involvement; today, they can be combined with synthetic insecticides to offer maximum protection.

Synthetic insecticides include indoor sprays, treated nets, repellents, and impregnated dog collars, all of which control sandflies. However, the use of these insecticides in endemic areas, such as India, has driven development of insecticide resistance in many sandfly vector species.³

As of 2020, 5 vaccines against Leishmania have been created. Two are approved–one in Brazil and one in Uzbekistan–for human use as immunotherapy, while the other 3 have been developed to immunize dogs in Brazil. However, the effectiveness of these vaccines is under debate. First, one of the vaccines used as immunotherapy for cutaneous leishmaniasis must be used in combination with conventional chemotherapy; second, long-term effects of the canine vaccine are unknown.¹ A preventive vaccine for humans is under development.^1,3

Final Thoughts

Leishmaniasis remains a notable parasitic disease that is increasing in prevalence worldwide. Clinicians should be aware of this disease because early detection and treatment are essential to control infection.³ Health care providers in the United States should be especially aware of this condition among patients who have a history of travel or migration; those in Texas should recognize the current endemic status of leishmaniasis there.^4,6

The genus Leishmania comprises protozoan parasites that cause approximately 2 million new cases of leishmaniasis each year across 98 countries.¹ These protozoa are obligate intracellular parasites of phlebotomine sandfly species that transmit leishmaniasis and result in a considerable parasitic cause of fatalities globally, second only to malaria.^2,3

Phlebotomine sandflies primarily live in tropical and subtropical regions and function as vectors for many pathogens in addition to Leishmania species, such as Bartonella species and arboviruses.³ In 2004, it was noted that the majority of leishmaniasis cases affected developing countries: 90% of visceral leishmaniasis cases occurred in Bangladesh, India, Nepal, Sudan, and Brazil, and 90% of cutaneous leishmaniasis cases occurred in Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia, and Syria.⁴ Of note, with recent environmental changes, phlebotomine sandflies have gradually migrated to more northerly latitudes, extending into Europe.⁵

Twenty Leishmania species and 30 sandfly species have been identified as causes of leishmaniasis.⁴Leishmania infection occurs when an infected sandfly bites a mammalian host and transmits the parasite’s flagellated form, known as a promastigote. Host inflammatory cells, such as monocytes and dendritic cells, phagocytize parasites that enter the skin. The interaction between parasites and dendritic cells become an important factor in the outcome of Leishmania infection in the host because dendritic cells promote development of CD4 and CD8 T lymphocytes with specificity to target Leishmania parasites and protect the host.¹

The number of cases of leishmaniasis has increased worldwide, most likely due to changes in the environment and human behaviors such as urbanization, the creation of new settlements, and migration from rural to urban areas.^3,5 Important risk factors in individual patients include malnutrition; low-quality housing and sanitation; a history of migration or travel; and immunosuppression, such as that caused by HIV co-infection.^2,5

Case Report

An otherwise healthy 25-year-old Bangladeshi man presented to our community hospital for evaluation of a painful leg ulcer of 1 month’s duration. The patient had migrated from Bangladesh to Panama, then to Costa Rica, followed by Guatemala, Honduras, Mexico, and, last, Texas. In Texas, he was identified by the US Immigration and Customs Enforcement, transported to a detention facility, and transferred to this hospital shortly afterward.

The patient reported that, during his extensive migration, he had lived in the jungle and reported what he described as mosquito bites on the legs. He subsequently developed a 3-cm ulcerated and crusted plaque with rolled borders on the right medial ankle (Figure 1). In addition, he had a palpable nodular cord on the medial leg from the ankle lesion to the mid thigh that was consistent with lymphocutaneous spread. Ultrasonography was negative for deep-vein thrombosis.

Because the patient’s recent migration from Central America was highly concerning for microbial infection, vancomycin and piperacillin-tazobactam were started empirically on admission. A punch biopsy from the right medial ankle was nondiagnostic, showing acute and chronic necrotizing inflammation along with numerous epithelioid histiocytes with a vaguely granulomatous appearance (Figure 2). A specimen from the right medial ankle that had already been taken by an astute border patrol medical provider was sent to the Centers for Disease Control and Prevention (CDC) for polymerase chain reaction analysis following admission and was found to be positive for Leishmania panamensis.

Given the concern for mucocutaneous leishmaniasis with this particular species, otolaryngology was consulted; however, the patient did not demonstrate mucocutaneous disease. Because of the elevated risk for persistent disease with L panamensis, systemic therapy was indicated and administered: IV amphotericin B 200 mg on days 1 through 5 and again on day 10. Improvement in the ulcer was seen after the 10-day regimen was completed.

Comment

Leishmaniasis can be broadly classified by geographic region or clinical presentation. Under the geographic region system, leishmaniasis can be categorized as Old World or New World. Old World leishmaniasis primarily is transmitted by Phlebotomus sandflies and carries the parasites Leishmania major and Leishmania tropica, among others. New World leishmaniasis is caused by Lutzomyia sandflies, which carry Leishmania mexicana, Leishmania braziliensis, Leishmania amazonensis, and others.⁶

Our patient presented with cutaneous leishmaniasis, one of 4 primary clinical disease forms of leishmaniasis; the other 3 forms under this classification system are diffuse cutaneous, mucocutaneous, and visceral leishmaniasis, also known as kala-azar.^3,6 Cutaneous leishmaniasis is limited to the skin, particularly the face and extremities. This form is more common with Old World vectors, with most cases occurring in Peru, Brazil, and the Middle East. In Old World cutaneous leishmaniasis, the disease begins with a solitary nodule at the site of the bite that ulcerates and can continue to spread in a sporotrichoid pattern. This cutaneous form tends to heal slowly over months to years with residual scarring. New World cutaneous leishmaniasis can present with a variety of clinical manifestations, including ulcerative, sarcoidlike, miliary, and nodular lesions.^6,7

The diffuse form of cutaneous leishmaniasis begins in a similar manner to the Old World cutaneous form: a single nodule spreads widely over the body, especially the nose, and covers the patient’s skin with keloidal or verrucous lesions that do not ulcerate. These nodules contain large groupings of Leishmania-filled foamy macrophages. Often, patients with diffuse cutaneous leishmaniasis are immunosuppressed and are unable to develop an immune response to leishmanin and other skin antigens.^6,7

Mucocutaneous leishmaniasis predominantly is caused by the New World species L braziliensis but also has been attributed to L amazonensis, L panamensis, and L guyanensis. This form manifests as mucosal lesions that can develop simultaneously with cutaneous lesions but more commonly appear months to years after resolution of the skin infection. Patients often present with ulceration of the lip, nose, and oropharynx, and destruction of the nasopharynx can result in severe consequences such as obstruction of the airway and perforation of the nasal septum (also known as espundia).^6,7

The most severe presentation of leishmaniasis is the visceral form (kala-azar), which presents with parasitic infection of the liver, spleen, and bone marrow. Most commonly caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi, this form has a long incubation period spanning months to years before presenting with diarrhea, hepatomegaly, splenomegaly, darkening of the skin (in Hindi, kala-azar means “black fever”), pancytopenia, lymphadenopathy, nephritis, and intestinal hemorrhage, among other severe manifestations. Visceral leishmaniasis has a poor prognosis: patients succumb to disease within 2 years if not treated.^6,7

Diagnosis—Diagnosing leishmaniasis starts with a complete personal and medical history, paying close attention to travel and exposures. Diagnosis is most successfully performed by polymerase chain reaction analysis, which is both highly sensitive and specific but also can be determined by culture using Novy-McNeal-Nicolle medium or by light microscopy. Histologic findings include the marquee sign, which describes an array of amastigotes (promastigotes that have developed into the intracellular tissue-stage form) with kinetoplasts surrounding the periphery of parasitized histiocytes. Giemsa staining can be helpful in identifying organisms.^2,6,7

The diagnosis in our case was challenging, as none of the above findings were seen in our patient. The specimen taken by the border patrol medical provider was negative on Gram, Giemsa, and Grocott-Gömöri methenamine silver staining; no amastigotes were identified. Another diagnostic modality (not performed in our patient) is the Montenegro delayed skin-reaction test, which often is positive in patients with cutaneous leishmaniasis but also yields a positive result in patients who have been cured of Leishmania infection.⁶

An important consideration in the diagnostic workup of leishmaniasis is that collaboration with the CDC can be helpful, such as in our case, as they provide clear guidance for specimen collection and processing.²

Treatment—Treating leishmaniasis is challenging and complex. Even the initial decision to treat depends on several factors, including the form of infection. Most visceral and mucocutaneous infections should be treated due to both the lack of self-resolution of these forms and the higher risk for a potentially life-threatening disease course; in contrast, cutaneous forms require further consideration before initiating treatment. Some indicators for treating cutaneous leishmaniasis include widespread infection, intention to decrease scarring, and lesions with the potential to cause further complications (eg, on the face or ears or close to joints).^6-8

The treatment of choice for cutaneous and mucocutaneous leishmaniasis is pentavalent antimony; however, this drug can only be obtained in the United States for investigational use, requiring approval by the CDC. A 20-day intravenous or intramuscular course of 20 mg/kg per day typically is used for cutaneous cases; a 28-day course typically is used for mucosal forms.

Amphotericin B is not only the treatment of choice for visceral leishmaniasis but also is an important alternative therapy for patients with mucosal leishmaniasis or who are co-infected with HIV. Patients with visceral infection also should receive supportive care for any concomitant afflictions, such as malnutrition or other infections. Although different regimens have been described, the US Food and Drug Administration has created outlines of specific intravenous infusion schedules for liposomal amphotericin B in immunocompetent and immunosuppressed patients.⁸ Liposomal amphotericin B also has a more favorable toxicity profile than conventional amphotericin B deoxycholate, which is otherwise effective in combating visceral leishmaniasis.^6-8

Other treatments that have been attempted include pentamidine, miltefosine, thermotherapy, oral itraconazole and fluconazole, rifampicin, metronidazole and cotrimoxazole, dapsone, photodynamic therapy, thermotherapy, topical paromomycin formulations, intralesional pentavalent antimony, and laser cryotherapy. Notable among these other agents is miltefosine, a US Food and Drug Administration–approved oral medication for adults and adolescents (used off-label for patients younger than 12 years) with cutaneous leishmaniasis caused by L braziliensis, L panamensis, or L guyanensis. Other oral options mentioned include the so-called azole antifungal medications, which historically have produced variable results. From the CDC’s reports, ketoconazole was moderately effective in Guatemala and Panama,⁸ whereas itraconazole did not demonstrate efficacy in Colombia, and the efficacy of fluconazole was inconsistent in different countries.⁸ When considering one of the local (as opposed to oral and parenteral) therapies mentioned, the extent of cutaneous findings as well as the risk of mucosal spread should be factored in.^6-8

Understandably, a number of considerations can come into play in determining the appropriate treatment modality, including body region affected, clinical form, severity, and Leishmania species.^6-8 Our case is of particular interest because it demonstrates the complexities behind the diagnosis and treatment of cutaneous leishmaniasis, with careful consideration geared toward the species; for example, because our patient was infected with L panamensis, which is known to cause mucocutaneous disease, the infectious disease service decided to pursue systemic therapy with amphotericin B rather than topical treatment.

Prevention—Vector control is the primary means of preventing leishmaniasis under 2 umbrellas: environmental management and synthetic insecticides. The goal of environmental management is to eliminate the phlebotomine sandfly habitat; this was the primary method of vector control until 1940. Until that time, tree stumps were removed, indoor cracks and crevices were filled to prevent sandfly emergence, and areas around animal shelters were cleaned. These methods were highly dependent on community awareness and involvement; today, they can be combined with synthetic insecticides to offer maximum protection.

Synthetic insecticides include indoor sprays, treated nets, repellents, and impregnated dog collars, all of which control sandflies. However, the use of these insecticides in endemic areas, such as India, has driven development of insecticide resistance in many sandfly vector species.³

As of 2020, 5 vaccines against Leishmania have been created. Two are approved–one in Brazil and one in Uzbekistan–for human use as immunotherapy, while the other 3 have been developed to immunize dogs in Brazil. However, the effectiveness of these vaccines is under debate. First, one of the vaccines used as immunotherapy for cutaneous leishmaniasis must be used in combination with conventional chemotherapy; second, long-term effects of the canine vaccine are unknown.¹ A preventive vaccine for humans is under development.^1,3

Final Thoughts

Leishmaniasis remains a notable parasitic disease that is increasing in prevalence worldwide. Clinicians should be aware of this disease because early detection and treatment are essential to control infection.³ Health care providers in the United States should be especially aware of this condition among patients who have a history of travel or migration; those in Texas should recognize the current endemic status of leishmaniasis there.^4,6

The genus Leishmania comprises protozoan parasites that cause approximately 2 million new cases of leishmaniasis each year across 98 countries.¹ These protozoa are obligate intracellular parasites of phlebotomine sandfly species that transmit leishmaniasis and result in a considerable parasitic cause of fatalities globally, second only to malaria.^2,3

Phlebotomine sandflies primarily live in tropical and subtropical regions and function as vectors for many pathogens in addition to Leishmania species, such as Bartonella species and arboviruses.³ In 2004, it was noted that the majority of leishmaniasis cases affected developing countries: 90% of visceral leishmaniasis cases occurred in Bangladesh, India, Nepal, Sudan, and Brazil, and 90% of cutaneous leishmaniasis cases occurred in Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia, and Syria.⁴ Of note, with recent environmental changes, phlebotomine sandflies have gradually migrated to more northerly latitudes, extending into Europe.⁵

Twenty Leishmania species and 30 sandfly species have been identified as causes of leishmaniasis.⁴Leishmania infection occurs when an infected sandfly bites a mammalian host and transmits the parasite’s flagellated form, known as a promastigote. Host inflammatory cells, such as monocytes and dendritic cells, phagocytize parasites that enter the skin. The interaction between parasites and dendritic cells become an important factor in the outcome of Leishmania infection in the host because dendritic cells promote development of CD4 and CD8 T lymphocytes with specificity to target Leishmania parasites and protect the host.¹

The number of cases of leishmaniasis has increased worldwide, most likely due to changes in the environment and human behaviors such as urbanization, the creation of new settlements, and migration from rural to urban areas.^3,5 Important risk factors in individual patients include malnutrition; low-quality housing and sanitation; a history of migration or travel; and immunosuppression, such as that caused by HIV co-infection.^2,5

Case Report

An otherwise healthy 25-year-old Bangladeshi man presented to our community hospital for evaluation of a painful leg ulcer of 1 month’s duration. The patient had migrated from Bangladesh to Panama, then to Costa Rica, followed by Guatemala, Honduras, Mexico, and, last, Texas. In Texas, he was identified by the US Immigration and Customs Enforcement, transported to a detention facility, and transferred to this hospital shortly afterward.

The patient reported that, during his extensive migration, he had lived in the jungle and reported what he described as mosquito bites on the legs. He subsequently developed a 3-cm ulcerated and crusted plaque with rolled borders on the right medial ankle (Figure 1). In addition, he had a palpable nodular cord on the medial leg from the ankle lesion to the mid thigh that was consistent with lymphocutaneous spread. Ultrasonography was negative for deep-vein thrombosis.

Because the patient’s recent migration from Central America was highly concerning for microbial infection, vancomycin and piperacillin-tazobactam were started empirically on admission. A punch biopsy from the right medial ankle was nondiagnostic, showing acute and chronic necrotizing inflammation along with numerous epithelioid histiocytes with a vaguely granulomatous appearance (Figure 2). A specimen from the right medial ankle that had already been taken by an astute border patrol medical provider was sent to the Centers for Disease Control and Prevention (CDC) for polymerase chain reaction analysis following admission and was found to be positive for Leishmania panamensis.

Given the concern for mucocutaneous leishmaniasis with this particular species, otolaryngology was consulted; however, the patient did not demonstrate mucocutaneous disease. Because of the elevated risk for persistent disease with L panamensis, systemic therapy was indicated and administered: IV amphotericin B 200 mg on days 1 through 5 and again on day 10. Improvement in the ulcer was seen after the 10-day regimen was completed.

Comment

Leishmaniasis can be broadly classified by geographic region or clinical presentation. Under the geographic region system, leishmaniasis can be categorized as Old World or New World. Old World leishmaniasis primarily is transmitted by Phlebotomus sandflies and carries the parasites Leishmania major and Leishmania tropica, among others. New World leishmaniasis is caused by Lutzomyia sandflies, which carry Leishmania mexicana, Leishmania braziliensis, Leishmania amazonensis, and others.⁶

Our patient presented with cutaneous leishmaniasis, one of 4 primary clinical disease forms of leishmaniasis; the other 3 forms under this classification system are diffuse cutaneous, mucocutaneous, and visceral leishmaniasis, also known as kala-azar.^3,6 Cutaneous leishmaniasis is limited to the skin, particularly the face and extremities. This form is more common with Old World vectors, with most cases occurring in Peru, Brazil, and the Middle East. In Old World cutaneous leishmaniasis, the disease begins with a solitary nodule at the site of the bite that ulcerates and can continue to spread in a sporotrichoid pattern. This cutaneous form tends to heal slowly over months to years with residual scarring. New World cutaneous leishmaniasis can present with a variety of clinical manifestations, including ulcerative, sarcoidlike, miliary, and nodular lesions.^6,7

The diffuse form of cutaneous leishmaniasis begins in a similar manner to the Old World cutaneous form: a single nodule spreads widely over the body, especially the nose, and covers the patient’s skin with keloidal or verrucous lesions that do not ulcerate. These nodules contain large groupings of Leishmania-filled foamy macrophages. Often, patients with diffuse cutaneous leishmaniasis are immunosuppressed and are unable to develop an immune response to leishmanin and other skin antigens.^6,7

Mucocutaneous leishmaniasis predominantly is caused by the New World species L braziliensis but also has been attributed to L amazonensis, L panamensis, and L guyanensis. This form manifests as mucosal lesions that can develop simultaneously with cutaneous lesions but more commonly appear months to years after resolution of the skin infection. Patients often present with ulceration of the lip, nose, and oropharynx, and destruction of the nasopharynx can result in severe consequences such as obstruction of the airway and perforation of the nasal septum (also known as espundia).^6,7

The most severe presentation of leishmaniasis is the visceral form (kala-azar), which presents with parasitic infection of the liver, spleen, and bone marrow. Most commonly caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi, this form has a long incubation period spanning months to years before presenting with diarrhea, hepatomegaly, splenomegaly, darkening of the skin (in Hindi, kala-azar means “black fever”), pancytopenia, lymphadenopathy, nephritis, and intestinal hemorrhage, among other severe manifestations. Visceral leishmaniasis has a poor prognosis: patients succumb to disease within 2 years if not treated.^6,7

Diagnosis—Diagnosing leishmaniasis starts with a complete personal and medical history, paying close attention to travel and exposures. Diagnosis is most successfully performed by polymerase chain reaction analysis, which is both highly sensitive and specific but also can be determined by culture using Novy-McNeal-Nicolle medium or by light microscopy. Histologic findings include the marquee sign, which describes an array of amastigotes (promastigotes that have developed into the intracellular tissue-stage form) with kinetoplasts surrounding the periphery of parasitized histiocytes. Giemsa staining can be helpful in identifying organisms.^2,6,7

The diagnosis in our case was challenging, as none of the above findings were seen in our patient. The specimen taken by the border patrol medical provider was negative on Gram, Giemsa, and Grocott-Gömöri methenamine silver staining; no amastigotes were identified. Another diagnostic modality (not performed in our patient) is the Montenegro delayed skin-reaction test, which often is positive in patients with cutaneous leishmaniasis but also yields a positive result in patients who have been cured of Leishmania infection.⁶

An important consideration in the diagnostic workup of leishmaniasis is that collaboration with the CDC can be helpful, such as in our case, as they provide clear guidance for specimen collection and processing.²

Treatment—Treating leishmaniasis is challenging and complex. Even the initial decision to treat depends on several factors, including the form of infection. Most visceral and mucocutaneous infections should be treated due to both the lack of self-resolution of these forms and the higher risk for a potentially life-threatening disease course; in contrast, cutaneous forms require further consideration before initiating treatment. Some indicators for treating cutaneous leishmaniasis include widespread infection, intention to decrease scarring, and lesions with the potential to cause further complications (eg, on the face or ears or close to joints).^6-8

The treatment of choice for cutaneous and mucocutaneous leishmaniasis is pentavalent antimony; however, this drug can only be obtained in the United States for investigational use, requiring approval by the CDC. A 20-day intravenous or intramuscular course of 20 mg/kg per day typically is used for cutaneous cases; a 28-day course typically is used for mucosal forms.

Amphotericin B is not only the treatment of choice for visceral leishmaniasis but also is an important alternative therapy for patients with mucosal leishmaniasis or who are co-infected with HIV. Patients with visceral infection also should receive supportive care for any concomitant afflictions, such as malnutrition or other infections. Although different regimens have been described, the US Food and Drug Administration has created outlines of specific intravenous infusion schedules for liposomal amphotericin B in immunocompetent and immunosuppressed patients.⁸ Liposomal amphotericin B also has a more favorable toxicity profile than conventional amphotericin B deoxycholate, which is otherwise effective in combating visceral leishmaniasis.^6-8

Other treatments that have been attempted include pentamidine, miltefosine, thermotherapy, oral itraconazole and fluconazole, rifampicin, metronidazole and cotrimoxazole, dapsone, photodynamic therapy, thermotherapy, topical paromomycin formulations, intralesional pentavalent antimony, and laser cryotherapy. Notable among these other agents is miltefosine, a US Food and Drug Administration–approved oral medication for adults and adolescents (used off-label for patients younger than 12 years) with cutaneous leishmaniasis caused by L braziliensis, L panamensis, or L guyanensis. Other oral options mentioned include the so-called azole antifungal medications, which historically have produced variable results. From the CDC’s reports, ketoconazole was moderately effective in Guatemala and Panama,⁸ whereas itraconazole did not demonstrate efficacy in Colombia, and the efficacy of fluconazole was inconsistent in different countries.⁸ When considering one of the local (as opposed to oral and parenteral) therapies mentioned, the extent of cutaneous findings as well as the risk of mucosal spread should be factored in.^6-8

Understandably, a number of considerations can come into play in determining the appropriate treatment modality, including body region affected, clinical form, severity, and Leishmania species.^6-8 Our case is of particular interest because it demonstrates the complexities behind the diagnosis and treatment of cutaneous leishmaniasis, with careful consideration geared toward the species; for example, because our patient was infected with L panamensis, which is known to cause mucocutaneous disease, the infectious disease service decided to pursue systemic therapy with amphotericin B rather than topical treatment.

Prevention—Vector control is the primary means of preventing leishmaniasis under 2 umbrellas: environmental management and synthetic insecticides. The goal of environmental management is to eliminate the phlebotomine sandfly habitat; this was the primary method of vector control until 1940. Until that time, tree stumps were removed, indoor cracks and crevices were filled to prevent sandfly emergence, and areas around animal shelters were cleaned. These methods were highly dependent on community awareness and involvement; today, they can be combined with synthetic insecticides to offer maximum protection.

Synthetic insecticides include indoor sprays, treated nets, repellents, and impregnated dog collars, all of which control sandflies. However, the use of these insecticides in endemic areas, such as India, has driven development of insecticide resistance in many sandfly vector species.³

As of 2020, 5 vaccines against Leishmania have been created. Two are approved–one in Brazil and one in Uzbekistan–for human use as immunotherapy, while the other 3 have been developed to immunize dogs in Brazil. However, the effectiveness of these vaccines is under debate. First, one of the vaccines used as immunotherapy for cutaneous leishmaniasis must be used in combination with conventional chemotherapy; second, long-term effects of the canine vaccine are unknown.¹ A preventive vaccine for humans is under development.^1,3

Final Thoughts

Leishmaniasis remains a notable parasitic disease that is increasing in prevalence worldwide. Clinicians should be aware of this disease because early detection and treatment are essential to control infection.³ Health care providers in the United States should be especially aware of this condition among patients who have a history of travel or migration; those in Texas should recognize the current endemic status of leishmaniasis there.^4,6

Incidence and Characteristics

The noble false widow spider (Steatoda nobilis) is one of the world’s most invasive spider species, having spread across the globe from Madeira and the Canary Islands into the North Atlantic.^1,2Steatoda comprise multiple species of false widow spiders, named for their resemblance to black widow spiders (Latrodectus). The noble false widow spider is the dominant species in buildings in southern Ireland and Great Britain, with a population surge in 2018 that caused multiple temporary school closures in London, England, for fumigation.³ The noble false widow spider was first documented in the United States in Ventura County, California, in 2011, with numerous specimens found in urban areas (eg, in parks, underneath garbage cans) closer to the coastline as well as farther inland. The species may have been introduced to this area by way of Port Hueneme, a city in California with a US naval base with routes to various other military bases in Western Europe.⁴ Given its already rapid expansion outside of the United States with a concurrent rise in bite reports, dermatologists should be familiar with these invasive and potentially dangerous arachnids.

The spread of noble false widow spiders is assisted by their wide range of temperature tolerance and ability to survive for months with little food and no water. They can live for several years, with one report of a noble false widow spider living up to 7 years.⁵ These spiders are found inside homes and buildings year-round, and they prefer to build their webs in an elevated position such as the top corner of a room. Steatoda weave tangle webs with crisscrossing threads that often have a denser middle section.⁵

Noble false widow spiders are sexually dimorphic, with males typically no larger than 1-cm long and females up to 1.4-cm long. They have a dark brown to black thorax and brown abdomen with red-brown legs. Males have brighter cream-colored abdominal markings than females, who lack markings altogether on their distinctive globular abdomen (Figure). The abdominal markings are known to resemble a skull or house.

©ePhotocorp / iStock / Getty Images Plus.

Although noble false widow spiders are not exclusively synanthropic, they can be found in any crevice in homes or other structures where there are humans such as office buildings.^5-7 Up until the last 20 years, reports of bites from noble false widow spiders worldwide were few and far between. In Great Britain, the spiders were first considered to be common in the 1980s, with recent evidence of an urban population boom in the last 5 to 10 years that has coincided with an increase in bite reports.^5,8,9

Clinical Significance

Most bites occur in a defensive manner, such as when humans perform activities that disturb the hiding space, cause vibrations in the web, or compress the body of the arachnid. Most envenomations in Great Britain occur while the individual is in bed, though they also may occur during other activities that disturb the spider, such as moving boxes or putting on a pair of pants.⁵ Occupational exposure to noble false widow spiders may soon be a concern for those involved in construction, carpentry, cleaning, and decorating given their recent invasive spread into the United States.

The venom from these spiders is neurotoxic and cytotoxic, causing moderate to intense pain that may resemble a wasp sting. The incidence of steatodism—which can include symptoms of pain in addition to fever, hypotension, headache, lethargy, nausea, localized diaphoresis, abdominal pain, paresthesias, and malaise—is unknown but reportedly rare.^5,10 There are considerable similarities between Steatoda and true black widow spider venom, which explains the symptom overlap with latrodectism. There are reports of severe debilitation lasting weeks due to pain and decreased affected limb movement after bites from noble false widow spiders.^10-12

Nearly all noble false widow spider bite reports describe immediate pain upon bite/envenomation, which is unlike the delayed pain from a black widow spider bite (after 10 minutes or more).^6,13,14 Erythema and swelling occur around a pale raised site of envenomation lasting up to 72 hours. The bite site may be highly tender and blister or ulcerate, with reports of cellulitis and local skin necrosis.^7,15 Pruritus during this period can be intense, and excoriation increases the risk for complications such as infection. Reports of anaphylaxis following a noble false widow spider bite are rare.^5,16 The incidence of bites may be underreported due to the lack of proper identification of the responsible arachnid for those who do not seek care or require hospitalization, though this is not unique to Steatoda.

There are reports of secondary infection after bites and even cases of limb amputation, septicemia, and death.^14,17 However, it is unknown if noble false widow spiders are vectors for bacteria transmitted during envenomation, and infection likely is secondary to scratching or inadequate wound care.^18,19 Potentially pathogenic bacteria have been isolated from the body surfaces of the noble false widow spider, including Pseudomonas putida, Staphylococcus capitis, and Staphylococcus epidermidis.²⁰ Fortunately, most captured cases (ie, events in which the biting arachnid was properly identified) report symptoms ranging from mild to moderate in severity without the need for hospitalization. A series of 24 reports revealed that all individuals experienced sharp pain upon the initial bite followed by erythema, and 18 of them experienced considerable swelling of the area soon thereafter. One individual experienced temporary paralysis of the affected limb, and 3 individuals experienced hypotension or hypertension in addition to fever, skin necrosis, or cellulitis.¹⁴

Treatment

The envenomation site should be washed with antibacterial soap and warm water and should be kept clean to prevent infection. There is no evidence that tight pressure bandaging of these bite sites will restrict venom flow; because it may worsen pain in the area, pressure bandaging is not recommended. When possible, the arachnid should be collected for identification. Supportive care is warranted for symptoms of pain, erythema, and swelling, with the use of cool compresses, oral pain relievers (eg, nonsteroidal anti-inflammatory drugs, acetaminophen), topical anesthetic (eg, lidocaine), or antihistamines as needed.

Urgent care is warranted for patients who experience severe symptoms of steatodism such as hypertension, lymphadenopathy, paresthesia, or limb paralysis. Limited reports show onset of this distress typically within an hour of envenomation. Treatments analogous to those for latrodectism including muscle relaxers and pain medications have demonstrated rapid attenuation of symptoms upon intramuscular administration of antivenom made from Latrodectus species.^21-23

Signs of infection warrant bacterial culture with antibiotic susceptibilities to ensure adequate treatment.²⁰ Infections from spider bites can present a few days to a week following envenomation. Symptoms may include spreading redness or an enlarging wound site, pus formation, worsening or unrelenting pain after 24 hours, fevers, flulike symptoms, and muscle cramps.

Final Thoughts

Symptoms from noble false widow spider bites range widely from localized pain, swelling, and erythema to ulceration, necrosis, and rarely death related to secondary infection. Because of their invasive spread in Europe and increasing presence in the United States, it is important to be aware of the possibility of noble false widow spider bites to manage reactions that may quickly lead to morbidity.

Incidence and Characteristics

The noble false widow spider (Steatoda nobilis) is one of the world’s most invasive spider species, having spread across the globe from Madeira and the Canary Islands into the North Atlantic.^1,2Steatoda comprise multiple species of false widow spiders, named for their resemblance to black widow spiders (Latrodectus). The noble false widow spider is the dominant species in buildings in southern Ireland and Great Britain, with a population surge in 2018 that caused multiple temporary school closures in London, England, for fumigation.³ The noble false widow spider was first documented in the United States in Ventura County, California, in 2011, with numerous specimens found in urban areas (eg, in parks, underneath garbage cans) closer to the coastline as well as farther inland. The species may have been introduced to this area by way of Port Hueneme, a city in California with a US naval base with routes to various other military bases in Western Europe.⁴ Given its already rapid expansion outside of the United States with a concurrent rise in bite reports, dermatologists should be familiar with these invasive and potentially dangerous arachnids.

The spread of noble false widow spiders is assisted by their wide range of temperature tolerance and ability to survive for months with little food and no water. They can live for several years, with one report of a noble false widow spider living up to 7 years.⁵ These spiders are found inside homes and buildings year-round, and they prefer to build their webs in an elevated position such as the top corner of a room. Steatoda weave tangle webs with crisscrossing threads that often have a denser middle section.⁵

Noble false widow spiders are sexually dimorphic, with males typically no larger than 1-cm long and females up to 1.4-cm long. They have a dark brown to black thorax and brown abdomen with red-brown legs. Males have brighter cream-colored abdominal markings than females, who lack markings altogether on their distinctive globular abdomen (Figure). The abdominal markings are known to resemble a skull or house.

©ePhotocorp / iStock / Getty Images Plus.

Although noble false widow spiders are not exclusively synanthropic, they can be found in any crevice in homes or other structures where there are humans such as office buildings.^5-7 Up until the last 20 years, reports of bites from noble false widow spiders worldwide were few and far between. In Great Britain, the spiders were first considered to be common in the 1980s, with recent evidence of an urban population boom in the last 5 to 10 years that has coincided with an increase in bite reports.^5,8,9

Clinical Significance

Most bites occur in a defensive manner, such as when humans perform activities that disturb the hiding space, cause vibrations in the web, or compress the body of the arachnid. Most envenomations in Great Britain occur while the individual is in bed, though they also may occur during other activities that disturb the spider, such as moving boxes or putting on a pair of pants.⁵ Occupational exposure to noble false widow spiders may soon be a concern for those involved in construction, carpentry, cleaning, and decorating given their recent invasive spread into the United States.

The venom from these spiders is neurotoxic and cytotoxic, causing moderate to intense pain that may resemble a wasp sting. The incidence of steatodism—which can include symptoms of pain in addition to fever, hypotension, headache, lethargy, nausea, localized diaphoresis, abdominal pain, paresthesias, and malaise—is unknown but reportedly rare.^5,10 There are considerable similarities between Steatoda and true black widow spider venom, which explains the symptom overlap with latrodectism. There are reports of severe debilitation lasting weeks due to pain and decreased affected limb movement after bites from noble false widow spiders.^10-12

Nearly all noble false widow spider bite reports describe immediate pain upon bite/envenomation, which is unlike the delayed pain from a black widow spider bite (after 10 minutes or more).^6,13,14 Erythema and swelling occur around a pale raised site of envenomation lasting up to 72 hours. The bite site may be highly tender and blister or ulcerate, with reports of cellulitis and local skin necrosis.^7,15 Pruritus during this period can be intense, and excoriation increases the risk for complications such as infection. Reports of anaphylaxis following a noble false widow spider bite are rare.^5,16 The incidence of bites may be underreported due to the lack of proper identification of the responsible arachnid for those who do not seek care or require hospitalization, though this is not unique to Steatoda.

There are reports of secondary infection after bites and even cases of limb amputation, septicemia, and death.^14,17 However, it is unknown if noble false widow spiders are vectors for bacteria transmitted during envenomation, and infection likely is secondary to scratching or inadequate wound care.^18,19 Potentially pathogenic bacteria have been isolated from the body surfaces of the noble false widow spider, including Pseudomonas putida, Staphylococcus capitis, and Staphylococcus epidermidis.²⁰ Fortunately, most captured cases (ie, events in which the biting arachnid was properly identified) report symptoms ranging from mild to moderate in severity without the need for hospitalization. A series of 24 reports revealed that all individuals experienced sharp pain upon the initial bite followed by erythema, and 18 of them experienced considerable swelling of the area soon thereafter. One individual experienced temporary paralysis of the affected limb, and 3 individuals experienced hypotension or hypertension in addition to fever, skin necrosis, or cellulitis.¹⁴

Treatment

The envenomation site should be washed with antibacterial soap and warm water and should be kept clean to prevent infection. There is no evidence that tight pressure bandaging of these bite sites will restrict venom flow; because it may worsen pain in the area, pressure bandaging is not recommended. When possible, the arachnid should be collected for identification. Supportive care is warranted for symptoms of pain, erythema, and swelling, with the use of cool compresses, oral pain relievers (eg, nonsteroidal anti-inflammatory drugs, acetaminophen), topical anesthetic (eg, lidocaine), or antihistamines as needed.

Urgent care is warranted for patients who experience severe symptoms of steatodism such as hypertension, lymphadenopathy, paresthesia, or limb paralysis. Limited reports show onset of this distress typically within an hour of envenomation. Treatments analogous to those for latrodectism including muscle relaxers and pain medications have demonstrated rapid attenuation of symptoms upon intramuscular administration of antivenom made from Latrodectus species.^21-23

Signs of infection warrant bacterial culture with antibiotic susceptibilities to ensure adequate treatment.²⁰ Infections from spider bites can present a few days to a week following envenomation. Symptoms may include spreading redness or an enlarging wound site, pus formation, worsening or unrelenting pain after 24 hours, fevers, flulike symptoms, and muscle cramps.

Final Thoughts

Symptoms from noble false widow spider bites range widely from localized pain, swelling, and erythema to ulceration, necrosis, and rarely death related to secondary infection. Because of their invasive spread in Europe and increasing presence in the United States, it is important to be aware of the possibility of noble false widow spider bites to manage reactions that may quickly lead to morbidity.

Incidence and Characteristics

The noble false widow spider (Steatoda nobilis) is one of the world’s most invasive spider species, having spread across the globe from Madeira and the Canary Islands into the North Atlantic.^1,2Steatoda comprise multiple species of false widow spiders, named for their resemblance to black widow spiders (Latrodectus). The noble false widow spider is the dominant species in buildings in southern Ireland and Great Britain, with a population surge in 2018 that caused multiple temporary school closures in London, England, for fumigation.³ The noble false widow spider was first documented in the United States in Ventura County, California, in 2011, with numerous specimens found in urban areas (eg, in parks, underneath garbage cans) closer to the coastline as well as farther inland. The species may have been introduced to this area by way of Port Hueneme, a city in California with a US naval base with routes to various other military bases in Western Europe.⁴ Given its already rapid expansion outside of the United States with a concurrent rise in bite reports, dermatologists should be familiar with these invasive and potentially dangerous arachnids.

The spread of noble false widow spiders is assisted by their wide range of temperature tolerance and ability to survive for months with little food and no water. They can live for several years, with one report of a noble false widow spider living up to 7 years.⁵ These spiders are found inside homes and buildings year-round, and they prefer to build their webs in an elevated position such as the top corner of a room. Steatoda weave tangle webs with crisscrossing threads that often have a denser middle section.⁵

Noble false widow spiders are sexually dimorphic, with males typically no larger than 1-cm long and females up to 1.4-cm long. They have a dark brown to black thorax and brown abdomen with red-brown legs. Males have brighter cream-colored abdominal markings than females, who lack markings altogether on their distinctive globular abdomen (Figure). The abdominal markings are known to resemble a skull or house.

©ePhotocorp / iStock / Getty Images Plus.

Although noble false widow spiders are not exclusively synanthropic, they can be found in any crevice in homes or other structures where there are humans such as office buildings.^5-7 Up until the last 20 years, reports of bites from noble false widow spiders worldwide were few and far between. In Great Britain, the spiders were first considered to be common in the 1980s, with recent evidence of an urban population boom in the last 5 to 10 years that has coincided with an increase in bite reports.^5,8,9

Clinical Significance

Most bites occur in a defensive manner, such as when humans perform activities that disturb the hiding space, cause vibrations in the web, or compress the body of the arachnid. Most envenomations in Great Britain occur while the individual is in bed, though they also may occur during other activities that disturb the spider, such as moving boxes or putting on a pair of pants.⁵ Occupational exposure to noble false widow spiders may soon be a concern for those involved in construction, carpentry, cleaning, and decorating given their recent invasive spread into the United States.

The venom from these spiders is neurotoxic and cytotoxic, causing moderate to intense pain that may resemble a wasp sting. The incidence of steatodism—which can include symptoms of pain in addition to fever, hypotension, headache, lethargy, nausea, localized diaphoresis, abdominal pain, paresthesias, and malaise—is unknown but reportedly rare.^5,10 There are considerable similarities between Steatoda and true black widow spider venom, which explains the symptom overlap with latrodectism. There are reports of severe debilitation lasting weeks due to pain and decreased affected limb movement after bites from noble false widow spiders.^10-12

Nearly all noble false widow spider bite reports describe immediate pain upon bite/envenomation, which is unlike the delayed pain from a black widow spider bite (after 10 minutes or more).^6,13,14 Erythema and swelling occur around a pale raised site of envenomation lasting up to 72 hours. The bite site may be highly tender and blister or ulcerate, with reports of cellulitis and local skin necrosis.^7,15 Pruritus during this period can be intense, and excoriation increases the risk for complications such as infection. Reports of anaphylaxis following a noble false widow spider bite are rare.^5,16 The incidence of bites may be underreported due to the lack of proper identification of the responsible arachnid for those who do not seek care or require hospitalization, though this is not unique to Steatoda.

There are reports of secondary infection after bites and even cases of limb amputation, septicemia, and death.^14,17 However, it is unknown if noble false widow spiders are vectors for bacteria transmitted during envenomation, and infection likely is secondary to scratching or inadequate wound care.^18,19 Potentially pathogenic bacteria have been isolated from the body surfaces of the noble false widow spider, including Pseudomonas putida, Staphylococcus capitis, and Staphylococcus epidermidis.²⁰ Fortunately, most captured cases (ie, events in which the biting arachnid was properly identified) report symptoms ranging from mild to moderate in severity without the need for hospitalization. A series of 24 reports revealed that all individuals experienced sharp pain upon the initial bite followed by erythema, and 18 of them experienced considerable swelling of the area soon thereafter. One individual experienced temporary paralysis of the affected limb, and 3 individuals experienced hypotension or hypertension in addition to fever, skin necrosis, or cellulitis.¹⁴

Treatment

The envenomation site should be washed with antibacterial soap and warm water and should be kept clean to prevent infection. There is no evidence that tight pressure bandaging of these bite sites will restrict venom flow; because it may worsen pain in the area, pressure bandaging is not recommended. When possible, the arachnid should be collected for identification. Supportive care is warranted for symptoms of pain, erythema, and swelling, with the use of cool compresses, oral pain relievers (eg, nonsteroidal anti-inflammatory drugs, acetaminophen), topical anesthetic (eg, lidocaine), or antihistamines as needed.

Urgent care is warranted for patients who experience severe symptoms of steatodism such as hypertension, lymphadenopathy, paresthesia, or limb paralysis. Limited reports show onset of this distress typically within an hour of envenomation. Treatments analogous to those for latrodectism including muscle relaxers and pain medications have demonstrated rapid attenuation of symptoms upon intramuscular administration of antivenom made from Latrodectus species.^21-23

Signs of infection warrant bacterial culture with antibiotic susceptibilities to ensure adequate treatment.²⁰ Infections from spider bites can present a few days to a week following envenomation. Symptoms may include spreading redness or an enlarging wound site, pus formation, worsening or unrelenting pain after 24 hours, fevers, flulike symptoms, and muscle cramps.

Final Thoughts

Symptoms from noble false widow spider bites range widely from localized pain, swelling, and erythema to ulceration, necrosis, and rarely death related to secondary infection. Because of their invasive spread in Europe and increasing presence in the United States, it is important to be aware of the possibility of noble false widow spider bites to manage reactions that may quickly lead to morbidity.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵