Dirk M. Elston, MD

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

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

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

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is an uncommon microangiopathy that presents with progressive telangiectases on the lower extremities that can eventually spread to involve the upper extremities and trunk. Systemic involvement is uncommon. The diagnosis is confirmed by biopsy, which demonstrates dilated capillaries and postcapillary venules with eosinophilic hyalinized walls. Treatment generally has focused on the use of vascular lasers.¹ We report a patient with advanced CCV and ocular involvement that responded to a combination of pulsed dye laser (PDL) therapy and sclerotherapy for cutaneous lesions.

A 63-year-old woman presented with partially blanchable, purple-black patches on the lower extremities (Figure 1). The upper extremities had minimal involvement at the time of presentation. A medical history revealed the lesions presented on the legs 10 years prior but were beginning to form on the arms. She had a history of hypertension and bleeding in the retina.

Histopathology revealed prominent dilation of postcapillary venules with eosinophilic collagenous materials in the vessel walls that was positive on periodic acid–Schiff stain, confirming the diagnosis of CCV. The perivascular collagenous material failed to stain with Congo red. Laboratory testing for serum protein electrophoresis, antinuclear antibodies, and baseline hematologic and metabolic panels revealed no abnormalities.

Over 3 years of treatment with PDL, most of the black patches resolved, but prominent telangiectatic vessels remained (Figure 2). Sclerotherapy with polidocanol (10 mg/mL) resulted in clearance of the majority of telangiectatic vessels. After each sclerotherapy treatment, Unna boots were applied for a minimum of 24 hours. The patient had no adverse effects from either PDL or sclerotherapy and was pleased with the results (Figure 3). An ophthalmologist had attributed the retinal bleeding to central serous chorioretinopathy, but tortuosity of superficial scleral and episcleral vessels progressed, suggesting CCV as the more likely cause (Figure 4). Currently, she is being followed for visual changes and further retinal bleeding.

Early CCV typically appears as blanchable pink or red macules, telangiectases, or petechiae on the lower extremities, progressing to involve the trunk and upper extremity.^1-3 In rare cases, CCV presents in a papular or annular variant instead of the typical telangiectatic form.^4,5 As the lesions progress, they often darken in appearance. Bleeding can occur, and the progressive patches are disfiguring.^6,7 Middle-aged to older adults typically present with CCV (range, 16–83 years), with a mean age of 62 years.^1,2,6 This disease affects both males and females, predominantly in White individuals.¹ Extracutaneous manifestations are rare.^1,2,6 One case of mucosal involvement was described in a patient with glossitis and oral erosions.⁸ We found no prior reports of nail or eye changes.^1,2

The etiology of CCV is unknown, but different theories have been proposed. One is that CCV is due to a genetic defect that changes collagen synthesis in the cutaneous microvasculature. Another more widely held belief is that CCV originates from an injury that occurs to the microvasculature endothelial cells. Regardless of the cause of the triggering injury, the result is induced intravascular occlusive microthrombi that cause perivascular fibrosis and endothelial hyperplasia.^2,6,7,9

Cutaneous collagenous vasculopathy may be influenced by systemic diseases. The most common comorbidities are hypertension, cardiovascular disease, diabetes mellitus, and hyperlipidemia.^1,3,6-8 The presentation of CCV with a malignancy is rare; 1 patient was diagnosed with multiple myeloma 18 months after CCV, and another patient’s cutaneous presentation led to discovery of pancreatic cancer with metastasis.^8,10 In this setting, the increased growth factors or hypercoagulability of malignancy may play a role in endothelial cell damage and hyperplasia. Autoimmune vascular injury also has been suggested to trigger CCV; 1 case involved antiribonucleoprotein antibodies, while another case involved anti–endothelial cell antibody assays.¹¹ In addition, CCV has been reported in hypercoagulable patients, demonstrating another route for endothelial damage, with 1 patient being heterozygous for prothrombin G20210A, a report of CCV in a patient with cryofibrinogenemia, and another patient being found positive for lupus anticoagulant.^11,12 Drugs also have been thought to influence CCV, including corticosteroids, lithium, thiothixene, interferon, isotretinoin, calcium channel blockers, antibiotics, hydroxyurea, and antidepressants.^7,11

The diagnosis of CCV is confirmed using light microscopy and collagen-specific immunostaining. Examination shows hyaline eosinophilic deposition of type IV collagen around the affected vessels, with the postcapillary venules showing characteristic duplication of the basal lamina.^3,9 The material stains positive with periodic acid-Schiff and Masson trichrome.³

Underreporting may contribute to the low incidence of CCV. The clinical presentation of CCV is similar to generalized essential telangiectasia, with biopsy distinguishing the two. Other diagnoses in the differential include hereditary hemorrhagic telangiectasia, which typically would have mucosal involvement; radiating telangiectatic mats and a strong family history; and hereditary benign telangiectasia, which typically presents in younger patients aged 1 year to adolescence.¹

Treatment with vascular lasers has been the main focus, using either the 595-nm PDL or the 1064-nm Nd:YAG laser.^6,13 Pulsed dye laser or intense pulsed light devices can improve patient well-being^1,2; intense pulsed light allows for a larger spot size and may be preferred in patients with a larger body surface area involved.¹³ However, a few other treatments have been proposed. One case report noted poor response to sclerotherapy.¹ In another case, a patient treated with a chemotherapy agent, bortezomib, for their concurrent multiple myeloma showed notable CCV cutaneous improvement. The proposed mechanism for bortezomib improving CCV is through its antiproliferative effect on endothelial cells of the superficial dermal vessels.⁸ Our patient did not achieve an adequate response with PDL, but the addition of sclerotherapy with polidocanol induced a successful response.

Patients should be examined for evidence of ocular involvement and referred to an ophthalmologist for appropriate care. Although there is no definite association with systemic illnesses or mediation, recent associations with an autoimmune disorder or underlying malignancy have been noted.^8,10,11 Age-appropriate cancer screening and attention to associated signs and symptoms are recommended.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is an uncommon microangiopathy that presents with progressive telangiectases on the lower extremities that can eventually spread to involve the upper extremities and trunk. Systemic involvement is uncommon. The diagnosis is confirmed by biopsy, which demonstrates dilated capillaries and postcapillary venules with eosinophilic hyalinized walls. Treatment generally has focused on the use of vascular lasers.¹ We report a patient with advanced CCV and ocular involvement that responded to a combination of pulsed dye laser (PDL) therapy and sclerotherapy for cutaneous lesions.

A 63-year-old woman presented with partially blanchable, purple-black patches on the lower extremities (Figure 1). The upper extremities had minimal involvement at the time of presentation. A medical history revealed the lesions presented on the legs 10 years prior but were beginning to form on the arms. She had a history of hypertension and bleeding in the retina.

Histopathology revealed prominent dilation of postcapillary venules with eosinophilic collagenous materials in the vessel walls that was positive on periodic acid–Schiff stain, confirming the diagnosis of CCV. The perivascular collagenous material failed to stain with Congo red. Laboratory testing for serum protein electrophoresis, antinuclear antibodies, and baseline hematologic and metabolic panels revealed no abnormalities.

Over 3 years of treatment with PDL, most of the black patches resolved, but prominent telangiectatic vessels remained (Figure 2). Sclerotherapy with polidocanol (10 mg/mL) resulted in clearance of the majority of telangiectatic vessels. After each sclerotherapy treatment, Unna boots were applied for a minimum of 24 hours. The patient had no adverse effects from either PDL or sclerotherapy and was pleased with the results (Figure 3). An ophthalmologist had attributed the retinal bleeding to central serous chorioretinopathy, but tortuosity of superficial scleral and episcleral vessels progressed, suggesting CCV as the more likely cause (Figure 4). Currently, she is being followed for visual changes and further retinal bleeding.

Early CCV typically appears as blanchable pink or red macules, telangiectases, or petechiae on the lower extremities, progressing to involve the trunk and upper extremity.^1-3 In rare cases, CCV presents in a papular or annular variant instead of the typical telangiectatic form.^4,5 As the lesions progress, they often darken in appearance. Bleeding can occur, and the progressive patches are disfiguring.^6,7 Middle-aged to older adults typically present with CCV (range, 16–83 years), with a mean age of 62 years.^1,2,6 This disease affects both males and females, predominantly in White individuals.¹ Extracutaneous manifestations are rare.^1,2,6 One case of mucosal involvement was described in a patient with glossitis and oral erosions.⁸ We found no prior reports of nail or eye changes.^1,2

The etiology of CCV is unknown, but different theories have been proposed. One is that CCV is due to a genetic defect that changes collagen synthesis in the cutaneous microvasculature. Another more widely held belief is that CCV originates from an injury that occurs to the microvasculature endothelial cells. Regardless of the cause of the triggering injury, the result is induced intravascular occlusive microthrombi that cause perivascular fibrosis and endothelial hyperplasia.^2,6,7,9

Cutaneous collagenous vasculopathy may be influenced by systemic diseases. The most common comorbidities are hypertension, cardiovascular disease, diabetes mellitus, and hyperlipidemia.^1,3,6-8 The presentation of CCV with a malignancy is rare; 1 patient was diagnosed with multiple myeloma 18 months after CCV, and another patient’s cutaneous presentation led to discovery of pancreatic cancer with metastasis.^8,10 In this setting, the increased growth factors or hypercoagulability of malignancy may play a role in endothelial cell damage and hyperplasia. Autoimmune vascular injury also has been suggested to trigger CCV; 1 case involved antiribonucleoprotein antibodies, while another case involved anti–endothelial cell antibody assays.¹¹ In addition, CCV has been reported in hypercoagulable patients, demonstrating another route for endothelial damage, with 1 patient being heterozygous for prothrombin G20210A, a report of CCV in a patient with cryofibrinogenemia, and another patient being found positive for lupus anticoagulant.^11,12 Drugs also have been thought to influence CCV, including corticosteroids, lithium, thiothixene, interferon, isotretinoin, calcium channel blockers, antibiotics, hydroxyurea, and antidepressants.^7,11

The diagnosis of CCV is confirmed using light microscopy and collagen-specific immunostaining. Examination shows hyaline eosinophilic deposition of type IV collagen around the affected vessels, with the postcapillary venules showing characteristic duplication of the basal lamina.^3,9 The material stains positive with periodic acid-Schiff and Masson trichrome.³

Underreporting may contribute to the low incidence of CCV. The clinical presentation of CCV is similar to generalized essential telangiectasia, with biopsy distinguishing the two. Other diagnoses in the differential include hereditary hemorrhagic telangiectasia, which typically would have mucosal involvement; radiating telangiectatic mats and a strong family history; and hereditary benign telangiectasia, which typically presents in younger patients aged 1 year to adolescence.¹

Treatment with vascular lasers has been the main focus, using either the 595-nm PDL or the 1064-nm Nd:YAG laser.^6,13 Pulsed dye laser or intense pulsed light devices can improve patient well-being^1,2; intense pulsed light allows for a larger spot size and may be preferred in patients with a larger body surface area involved.¹³ However, a few other treatments have been proposed. One case report noted poor response to sclerotherapy.¹ In another case, a patient treated with a chemotherapy agent, bortezomib, for their concurrent multiple myeloma showed notable CCV cutaneous improvement. The proposed mechanism for bortezomib improving CCV is through its antiproliferative effect on endothelial cells of the superficial dermal vessels.⁸ Our patient did not achieve an adequate response with PDL, but the addition of sclerotherapy with polidocanol induced a successful response.

Patients should be examined for evidence of ocular involvement and referred to an ophthalmologist for appropriate care. Although there is no definite association with systemic illnesses or mediation, recent associations with an autoimmune disorder or underlying malignancy have been noted.^8,10,11 Age-appropriate cancer screening and attention to associated signs and symptoms are recommended.

To the Editor:

Cutaneous collagenous vasculopathy (CCV) is an uncommon microangiopathy that presents with progressive telangiectases on the lower extremities that can eventually spread to involve the upper extremities and trunk. Systemic involvement is uncommon. The diagnosis is confirmed by biopsy, which demonstrates dilated capillaries and postcapillary venules with eosinophilic hyalinized walls. Treatment generally has focused on the use of vascular lasers.¹ We report a patient with advanced CCV and ocular involvement that responded to a combination of pulsed dye laser (PDL) therapy and sclerotherapy for cutaneous lesions.

A 63-year-old woman presented with partially blanchable, purple-black patches on the lower extremities (Figure 1). The upper extremities had minimal involvement at the time of presentation. A medical history revealed the lesions presented on the legs 10 years prior but were beginning to form on the arms. She had a history of hypertension and bleeding in the retina.

Histopathology revealed prominent dilation of postcapillary venules with eosinophilic collagenous materials in the vessel walls that was positive on periodic acid–Schiff stain, confirming the diagnosis of CCV. The perivascular collagenous material failed to stain with Congo red. Laboratory testing for serum protein electrophoresis, antinuclear antibodies, and baseline hematologic and metabolic panels revealed no abnormalities.

Over 3 years of treatment with PDL, most of the black patches resolved, but prominent telangiectatic vessels remained (Figure 2). Sclerotherapy with polidocanol (10 mg/mL) resulted in clearance of the majority of telangiectatic vessels. After each sclerotherapy treatment, Unna boots were applied for a minimum of 24 hours. The patient had no adverse effects from either PDL or sclerotherapy and was pleased with the results (Figure 3). An ophthalmologist had attributed the retinal bleeding to central serous chorioretinopathy, but tortuosity of superficial scleral and episcleral vessels progressed, suggesting CCV as the more likely cause (Figure 4). Currently, she is being followed for visual changes and further retinal bleeding.

Early CCV typically appears as blanchable pink or red macules, telangiectases, or petechiae on the lower extremities, progressing to involve the trunk and upper extremity.^1-3 In rare cases, CCV presents in a papular or annular variant instead of the typical telangiectatic form.^4,5 As the lesions progress, they often darken in appearance. Bleeding can occur, and the progressive patches are disfiguring.^6,7 Middle-aged to older adults typically present with CCV (range, 16–83 years), with a mean age of 62 years.^1,2,6 This disease affects both males and females, predominantly in White individuals.¹ Extracutaneous manifestations are rare.^1,2,6 One case of mucosal involvement was described in a patient with glossitis and oral erosions.⁸ We found no prior reports of nail or eye changes.^1,2

The etiology of CCV is unknown, but different theories have been proposed. One is that CCV is due to a genetic defect that changes collagen synthesis in the cutaneous microvasculature. Another more widely held belief is that CCV originates from an injury that occurs to the microvasculature endothelial cells. Regardless of the cause of the triggering injury, the result is induced intravascular occlusive microthrombi that cause perivascular fibrosis and endothelial hyperplasia.^2,6,7,9

Cutaneous collagenous vasculopathy may be influenced by systemic diseases. The most common comorbidities are hypertension, cardiovascular disease, diabetes mellitus, and hyperlipidemia.^1,3,6-8 The presentation of CCV with a malignancy is rare; 1 patient was diagnosed with multiple myeloma 18 months after CCV, and another patient’s cutaneous presentation led to discovery of pancreatic cancer with metastasis.^8,10 In this setting, the increased growth factors or hypercoagulability of malignancy may play a role in endothelial cell damage and hyperplasia. Autoimmune vascular injury also has been suggested to trigger CCV; 1 case involved antiribonucleoprotein antibodies, while another case involved anti–endothelial cell antibody assays.¹¹ In addition, CCV has been reported in hypercoagulable patients, demonstrating another route for endothelial damage, with 1 patient being heterozygous for prothrombin G20210A, a report of CCV in a patient with cryofibrinogenemia, and another patient being found positive for lupus anticoagulant.^11,12 Drugs also have been thought to influence CCV, including corticosteroids, lithium, thiothixene, interferon, isotretinoin, calcium channel blockers, antibiotics, hydroxyurea, and antidepressants.^7,11

The diagnosis of CCV is confirmed using light microscopy and collagen-specific immunostaining. Examination shows hyaline eosinophilic deposition of type IV collagen around the affected vessels, with the postcapillary venules showing characteristic duplication of the basal lamina.^3,9 The material stains positive with periodic acid-Schiff and Masson trichrome.³

Underreporting may contribute to the low incidence of CCV. The clinical presentation of CCV is similar to generalized essential telangiectasia, with biopsy distinguishing the two. Other diagnoses in the differential include hereditary hemorrhagic telangiectasia, which typically would have mucosal involvement; radiating telangiectatic mats and a strong family history; and hereditary benign telangiectasia, which typically presents in younger patients aged 1 year to adolescence.¹

Treatment with vascular lasers has been the main focus, using either the 595-nm PDL or the 1064-nm Nd:YAG laser.^6,13 Pulsed dye laser or intense pulsed light devices can improve patient well-being^1,2; intense pulsed light allows for a larger spot size and may be preferred in patients with a larger body surface area involved.¹³ However, a few other treatments have been proposed. One case report noted poor response to sclerotherapy.¹ In another case, a patient treated with a chemotherapy agent, bortezomib, for their concurrent multiple myeloma showed notable CCV cutaneous improvement. The proposed mechanism for bortezomib improving CCV is through its antiproliferative effect on endothelial cells of the superficial dermal vessels.⁸ Our patient did not achieve an adequate response with PDL, but the addition of sclerotherapy with polidocanol induced a successful response.

Patients should be examined for evidence of ocular involvement and referred to an ophthalmologist for appropriate care. Although there is no definite association with systemic illnesses or mediation, recent associations with an autoimmune disorder or underlying malignancy have been noted.^8,10,11 Age-appropriate cancer screening and attention to associated signs and symptoms are recommended.

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

Cutaneous Manifestations

Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.¹

Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.²Capsicum peppers also have induced allergic contact dermatitis in a food production worker.³

Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.⁴

Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.^5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.⁷ Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.

Obtaining Relief

Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.⁸ Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.⁹

Identifying Features and Plant Facts

The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000 bc.¹⁰ On the Scoville scale, which was developed to quantify the hotness of foods and spices, Capsicum peppers are rated at approximately 2 million units; by comparison, jalapeño peppers have a Scoville score of 4500¹¹ and capsaicin isolate has a score of 16 million units. Capsicum species rank among the hottest peppers in the world.

Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.¹² Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.

Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.¹³ Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.¹⁴ Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.¹⁵

Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.¹ Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.

Medicinal Use

On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,⁵ postherpetic neuralgia,⁶ psoriasis,¹⁶ and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,¹⁷ fibromyalgia,¹⁸ migraines,¹⁴ cluster headaches,⁹ and HIV-associated distal sensory neuropathy.⁵

Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.¹⁹ The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.¹¹ Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.^20,21

Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.²² The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.²³

Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.^19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.²⁷ Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.

Final Thoughts

Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.

Cutaneous Manifestations

Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.¹

Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.²Capsicum peppers also have induced allergic contact dermatitis in a food production worker.³

Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.⁴

Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.^5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.⁷ Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.

Obtaining Relief

Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.⁸ Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.⁹

Identifying Features and Plant Facts

The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000 bc.¹⁰ On the Scoville scale, which was developed to quantify the hotness of foods and spices, Capsicum peppers are rated at approximately 2 million units; by comparison, jalapeño peppers have a Scoville score of 4500¹¹ and capsaicin isolate has a score of 16 million units. Capsicum species rank among the hottest peppers in the world.

Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.¹² Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.

Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.¹³ Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.¹⁴ Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.¹⁵

Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.¹ Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.

Medicinal Use

On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,⁵ postherpetic neuralgia,⁶ psoriasis,¹⁶ and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,¹⁷ fibromyalgia,¹⁸ migraines,¹⁴ cluster headaches,⁹ and HIV-associated distal sensory neuropathy.⁵

Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.¹⁹ The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.¹¹ Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.^20,21

Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.²² The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.²³

Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.^19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.²⁷ Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.

Final Thoughts

Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.

Cutaneous Manifestations

Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.¹

Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.²Capsicum peppers also have induced allergic contact dermatitis in a food production worker.³

Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.⁴

Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.^5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.⁷ Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.

Obtaining Relief

Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.⁸ Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.⁹

Identifying Features and Plant Facts

The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000 bc.¹⁰ On the Scoville scale, which was developed to quantify the hotness of foods and spices, Capsicum peppers are rated at approximately 2 million units; by comparison, jalapeño peppers have a Scoville score of 4500¹¹ and capsaicin isolate has a score of 16 million units. Capsicum species rank among the hottest peppers in the world.

Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.¹² Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.

Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.¹³ Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.¹⁴ Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.¹⁵

Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.¹ Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.

Medicinal Use

On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,⁵ postherpetic neuralgia,⁶ psoriasis,¹⁶ and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,¹⁷ fibromyalgia,¹⁸ migraines,¹⁴ cluster headaches,⁹ and HIV-associated distal sensory neuropathy.⁵

Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.¹⁹ The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.¹¹ Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.^20,21

Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.²² The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.²³

Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.^19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.²⁷ Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.

Final Thoughts

Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.

Contact dermatitis is a common problem in the floral bulb industry and is considered an occupational disease. Daffodils (Narcissus species)(Figure) are thought to be the most common cause of irritant contact dermatitis among florists.¹

Clinical Importance

Picking daffodils can start as early as October, when the flowers are still closed. The picker’s hand slides down the stem to snap the stalk at the base. This potentially traumatic maneuver to the web of the fingers leads to abrasions, which are irritated by the sap and cause granulomatous sores and paronychia. An experienced picker can pick 20,000 flowers a day, leading to extensive contact with sap.²

Eczematous or granulomatous rash on the arms also is seen as the sap irritates the wrist and forearm. The pickers often hold the flowers until a bunch of 10 has been collected. The 10 flowers are held together by a rubber band and stacked along the arm, the chin, and the axilla, causing the rash to extend to those areas. Sap also can be transferred by the hand to other parts of the body, such as the face. In men, sap can be transferred to the genitalia as the men urinate in the field.

Narcissus also can cause poisoning if ingested by humans or animals. Researchers who analyzed calls made to the New Zealand Natural Poisons Centre between 2003 and 2010 determined that daffodil was the 11th most common call for plant-related poisoning.³

Although the severity of plant poisoning often is low due to the small amount of plant material usually consumed, more severe poisoning can occur when the plant is eaten for medicinal purposes or mistaken for an edible plant.³ Vomiting, respiratory symptoms, abdominal pain, diarrhea, trembling, and convulsions can occur when daffodils are ingested. Death has been reported due to ingestion of the bulbs.⁴

In February 2010, 10 children aged 10 and 11 years and their 22-year-old guide presented to an emergency department in Israel after ingesting Narcissus bulbs, which were mistakenly believed to be the bulbs of onions.⁴ Eight children and the guide vomited. One child and the guide reported abdominal pain. All were discharged in stable condition after 4 hours of observation.⁴

Clinical Manifestations

Daffodil rash or lily rash was first described in 1910.⁵ The typical rash presents as dryness, fissures, scaling, and erythema of the fingertips, hands, and forearms, often with subungual hyperkeratosis. Vesicles and pustules may be seen. The rash may extend to other areas of the body, including the face.⁶

Use of protective gloves and clothing to avoid contact with the plant is recommended.² Treatment includes stopping contact with the irritant, eye irrigation, and supportive measures (airway, breathing, and circulation). Activated charcoal can be helpful if used within 1 hour after ingestion but is contraindicated in vomiting patients.⁴

Identifying Features

The genus Narcissus is in the family Amaryllidaceae and contains ornamental plants, including daffodil (trumpet Narcissus, Narcissus pseudonarcissus), jonquil (Narcissus jonquilla), and poet’s narcissus (Narcissus poeticus). Most species are perennial; the plant emerges from a bulb in spring. Leaves originate from the base of the plant and range from 5-cm to 1.2-meters long, depending on the species. The flowers span a range of shapes and colors—from a trumpet (the daffodil) to a ringlike cup (poet’s Narcissus) and in yellow, white, and pink.⁷

Distribution and Plant Facts

Distribution—There are approximately 80 to 100 wild Narcissus species, which are found in southwestern Europe, North Africa, the Balkan Peninsula, Italy, and France. There are more than 27,000 Narcissus cultivars registered in the International Daffodil Register.⁸

Plant Facts—The daffodil is the national flower of Wales. It also is often used to depict hope and joy and is the symbol of cancer charities in many countries.⁹

The name Narcissus is believed to have originated from Greek mythology. A handsome youth, Narcissus, fell in love with his own reflection, for which the gods punished him by turning him into a flower.¹⁰

Another theory states that Narcissus is derived from the Greek word narkao (to benumb) due to its narcotic properties. When an open wound is subjected to an extract of the bulb, numbness of the entire nervous system is said to occur as well as paralysis of the heart. This narcotic effect led Socrates to refer to the Narcissus plant as the “chaplet of the infernal gods.”¹¹

Narcissus is an important flower in various ethnic rituals. The Greeks often planted daffodils near tombs. In Muslim culture, white is believed to be the symbol of good and purity; Narcissus was one of the most common white-flowered plants found in Muslim graveyards.¹²

Medicinal Qualities and Uses—Narcissus species have been used as medicinal plants for a variety of ailments. For example, Narcissus tazetta contains flavonoids, alkaloids, saponins, tannins, cardiac glycosides, oil, steroids, terpenoids, and anthraquinones that contribute to its antibacterial, antifungal, antiviral, antimalarial, anticancer, antioxidant, dermatologic, cardiovascular, immunomodulatory, and acetylcholinesterase inhibitory effects.¹³ In a study, chloroform extracts from N tazetta bulbs were found to be more active than doxorubicin against hepatocellular and colon cancer cell lines.¹⁴

More than 500 alkaloids have been isolated from the Narcissus genus.¹⁵ In 2001, the US Food and Drug Administration approved one of the alkaloids, galantamine, for the treatment of mild to moderate stages of Alzheimer disease.¹⁶ Galantamine selectively and reversibly inhibits acetylcholinesterase, the enzyme believed responsible for neurodegeneration seen in Alzheimer disease. Plants are the main source of galantamine, despite the ability of pharmaceutical companies to synthesize the compound. Galantamine hydrobromide is sold by prescription (Razadyne [Janssen Pharmaceuticals, Inc]); generic formulations approved by the US Food and Drug Administration have been produced by more than 15 pharmaceutical companies.^17,18

Irritant and Allergen

Sap found in the bulbs and hollow stems of Narcissus contains calcium oxalate crystals, or raphides. The minute, needle-shaped calcium oxalate crystals are believed to be a waste product of cellular metabolism.¹⁹ When the plant structure is compromised by pickers snapping the stalk, the sharp crystals penetrate the skin to cause an irritant contact dermatitis.

Relevant Research—A study used electron microscopy to characterize the structure of raphides from various plants,² though not from Narcissus species; the structure of each raphide was then compared to the degree of irritation it produced. The researchers concluded that more elongated crystals (those containing barbs) produce a greater degree of irritation. Narcissus species are known to cause varying degrees of skin irritation: For example, N tazetta rarely causes skin irritation, whereas N pseudonarcissi (daffodil) tends to cause remarkably more skin irritation.²

Allergic reactions to and strong toxicity from Narcissus species are not well understood. In a study, only 2 alkaloids—homolycorine and masonin—produced a weakly positive reaction in patch tests on sensitized guinea pigs, which correlates with the finding of a different study, in which only 2 of 12 patients whose findings were examined over 14 years had a positive patch test for Narcissus.^20,21

However, IgE-mediated allergies indicative of an allergic response to Narcissus have been reported. A study isolated an allergenic protein, narcin, from bulbs of N tazetta. Narcin is a 13-kDa protein with potent allergenic effects capable of inducing production of proinflammatory cytokines and increasing IgE levels in mononuclear cells in peripheral blood.²²

More research is required to find and understand the compounds responsible for causing an allergic reaction to Narcissus.

Contact dermatitis is a common problem in the floral bulb industry and is considered an occupational disease. Daffodils (Narcissus species)(Figure) are thought to be the most common cause of irritant contact dermatitis among florists.¹

Clinical Importance

Picking daffodils can start as early as October, when the flowers are still closed. The picker’s hand slides down the stem to snap the stalk at the base. This potentially traumatic maneuver to the web of the fingers leads to abrasions, which are irritated by the sap and cause granulomatous sores and paronychia. An experienced picker can pick 20,000 flowers a day, leading to extensive contact with sap.²

Eczematous or granulomatous rash on the arms also is seen as the sap irritates the wrist and forearm. The pickers often hold the flowers until a bunch of 10 has been collected. The 10 flowers are held together by a rubber band and stacked along the arm, the chin, and the axilla, causing the rash to extend to those areas. Sap also can be transferred by the hand to other parts of the body, such as the face. In men, sap can be transferred to the genitalia as the men urinate in the field.

Narcissus also can cause poisoning if ingested by humans or animals. Researchers who analyzed calls made to the New Zealand Natural Poisons Centre between 2003 and 2010 determined that daffodil was the 11th most common call for plant-related poisoning.³

Although the severity of plant poisoning often is low due to the small amount of plant material usually consumed, more severe poisoning can occur when the plant is eaten for medicinal purposes or mistaken for an edible plant.³ Vomiting, respiratory symptoms, abdominal pain, diarrhea, trembling, and convulsions can occur when daffodils are ingested. Death has been reported due to ingestion of the bulbs.⁴

In February 2010, 10 children aged 10 and 11 years and their 22-year-old guide presented to an emergency department in Israel after ingesting Narcissus bulbs, which were mistakenly believed to be the bulbs of onions.⁴ Eight children and the guide vomited. One child and the guide reported abdominal pain. All were discharged in stable condition after 4 hours of observation.⁴

Clinical Manifestations

Daffodil rash or lily rash was first described in 1910.⁵ The typical rash presents as dryness, fissures, scaling, and erythema of the fingertips, hands, and forearms, often with subungual hyperkeratosis. Vesicles and pustules may be seen. The rash may extend to other areas of the body, including the face.⁶

Use of protective gloves and clothing to avoid contact with the plant is recommended.² Treatment includes stopping contact with the irritant, eye irrigation, and supportive measures (airway, breathing, and circulation). Activated charcoal can be helpful if used within 1 hour after ingestion but is contraindicated in vomiting patients.⁴

Identifying Features

The genus Narcissus is in the family Amaryllidaceae and contains ornamental plants, including daffodil (trumpet Narcissus, Narcissus pseudonarcissus), jonquil (Narcissus jonquilla), and poet’s narcissus (Narcissus poeticus). Most species are perennial; the plant emerges from a bulb in spring. Leaves originate from the base of the plant and range from 5-cm to 1.2-meters long, depending on the species. The flowers span a range of shapes and colors—from a trumpet (the daffodil) to a ringlike cup (poet’s Narcissus) and in yellow, white, and pink.⁷

Distribution and Plant Facts

Distribution—There are approximately 80 to 100 wild Narcissus species, which are found in southwestern Europe, North Africa, the Balkan Peninsula, Italy, and France. There are more than 27,000 Narcissus cultivars registered in the International Daffodil Register.⁸

Plant Facts—The daffodil is the national flower of Wales. It also is often used to depict hope and joy and is the symbol of cancer charities in many countries.⁹

The name Narcissus is believed to have originated from Greek mythology. A handsome youth, Narcissus, fell in love with his own reflection, for which the gods punished him by turning him into a flower.¹⁰

Another theory states that Narcissus is derived from the Greek word narkao (to benumb) due to its narcotic properties. When an open wound is subjected to an extract of the bulb, numbness of the entire nervous system is said to occur as well as paralysis of the heart. This narcotic effect led Socrates to refer to the Narcissus plant as the “chaplet of the infernal gods.”¹¹

Narcissus is an important flower in various ethnic rituals. The Greeks often planted daffodils near tombs. In Muslim culture, white is believed to be the symbol of good and purity; Narcissus was one of the most common white-flowered plants found in Muslim graveyards.¹²

Medicinal Qualities and Uses—Narcissus species have been used as medicinal plants for a variety of ailments. For example, Narcissus tazetta contains flavonoids, alkaloids, saponins, tannins, cardiac glycosides, oil, steroids, terpenoids, and anthraquinones that contribute to its antibacterial, antifungal, antiviral, antimalarial, anticancer, antioxidant, dermatologic, cardiovascular, immunomodulatory, and acetylcholinesterase inhibitory effects.¹³ In a study, chloroform extracts from N tazetta bulbs were found to be more active than doxorubicin against hepatocellular and colon cancer cell lines.¹⁴

More than 500 alkaloids have been isolated from the Narcissus genus.¹⁵ In 2001, the US Food and Drug Administration approved one of the alkaloids, galantamine, for the treatment of mild to moderate stages of Alzheimer disease.¹⁶ Galantamine selectively and reversibly inhibits acetylcholinesterase, the enzyme believed responsible for neurodegeneration seen in Alzheimer disease. Plants are the main source of galantamine, despite the ability of pharmaceutical companies to synthesize the compound. Galantamine hydrobromide is sold by prescription (Razadyne [Janssen Pharmaceuticals, Inc]); generic formulations approved by the US Food and Drug Administration have been produced by more than 15 pharmaceutical companies.^17,18

Irritant and Allergen

Sap found in the bulbs and hollow stems of Narcissus contains calcium oxalate crystals, or raphides. The minute, needle-shaped calcium oxalate crystals are believed to be a waste product of cellular metabolism.¹⁹ When the plant structure is compromised by pickers snapping the stalk, the sharp crystals penetrate the skin to cause an irritant contact dermatitis.

Relevant Research—A study used electron microscopy to characterize the structure of raphides from various plants,² though not from Narcissus species; the structure of each raphide was then compared to the degree of irritation it produced. The researchers concluded that more elongated crystals (those containing barbs) produce a greater degree of irritation. Narcissus species are known to cause varying degrees of skin irritation: For example, N tazetta rarely causes skin irritation, whereas N pseudonarcissi (daffodil) tends to cause remarkably more skin irritation.²

Allergic reactions to and strong toxicity from Narcissus species are not well understood. In a study, only 2 alkaloids—homolycorine and masonin—produced a weakly positive reaction in patch tests on sensitized guinea pigs, which correlates with the finding of a different study, in which only 2 of 12 patients whose findings were examined over 14 years had a positive patch test for Narcissus.^20,21

However, IgE-mediated allergies indicative of an allergic response to Narcissus have been reported. A study isolated an allergenic protein, narcin, from bulbs of N tazetta. Narcin is a 13-kDa protein with potent allergenic effects capable of inducing production of proinflammatory cytokines and increasing IgE levels in mononuclear cells in peripheral blood.²²

More research is required to find and understand the compounds responsible for causing an allergic reaction to Narcissus.

Contact dermatitis is a common problem in the floral bulb industry and is considered an occupational disease. Daffodils (Narcissus species)(Figure) are thought to be the most common cause of irritant contact dermatitis among florists.¹

Clinical Importance

Picking daffodils can start as early as October, when the flowers are still closed. The picker’s hand slides down the stem to snap the stalk at the base. This potentially traumatic maneuver to the web of the fingers leads to abrasions, which are irritated by the sap and cause granulomatous sores and paronychia. An experienced picker can pick 20,000 flowers a day, leading to extensive contact with sap.²

Eczematous or granulomatous rash on the arms also is seen as the sap irritates the wrist and forearm. The pickers often hold the flowers until a bunch of 10 has been collected. The 10 flowers are held together by a rubber band and stacked along the arm, the chin, and the axilla, causing the rash to extend to those areas. Sap also can be transferred by the hand to other parts of the body, such as the face. In men, sap can be transferred to the genitalia as the men urinate in the field.

Narcissus also can cause poisoning if ingested by humans or animals. Researchers who analyzed calls made to the New Zealand Natural Poisons Centre between 2003 and 2010 determined that daffodil was the 11th most common call for plant-related poisoning.³

Although the severity of plant poisoning often is low due to the small amount of plant material usually consumed, more severe poisoning can occur when the plant is eaten for medicinal purposes or mistaken for an edible plant.³ Vomiting, respiratory symptoms, abdominal pain, diarrhea, trembling, and convulsions can occur when daffodils are ingested. Death has been reported due to ingestion of the bulbs.⁴

In February 2010, 10 children aged 10 and 11 years and their 22-year-old guide presented to an emergency department in Israel after ingesting Narcissus bulbs, which were mistakenly believed to be the bulbs of onions.⁴ Eight children and the guide vomited. One child and the guide reported abdominal pain. All were discharged in stable condition after 4 hours of observation.⁴

Clinical Manifestations

Daffodil rash or lily rash was first described in 1910.⁵ The typical rash presents as dryness, fissures, scaling, and erythema of the fingertips, hands, and forearms, often with subungual hyperkeratosis. Vesicles and pustules may be seen. The rash may extend to other areas of the body, including the face.⁶

Use of protective gloves and clothing to avoid contact with the plant is recommended.² Treatment includes stopping contact with the irritant, eye irrigation, and supportive measures (airway, breathing, and circulation). Activated charcoal can be helpful if used within 1 hour after ingestion but is contraindicated in vomiting patients.⁴

Identifying Features

The genus Narcissus is in the family Amaryllidaceae and contains ornamental plants, including daffodil (trumpet Narcissus, Narcissus pseudonarcissus), jonquil (Narcissus jonquilla), and poet’s narcissus (Narcissus poeticus). Most species are perennial; the plant emerges from a bulb in spring. Leaves originate from the base of the plant and range from 5-cm to 1.2-meters long, depending on the species. The flowers span a range of shapes and colors—from a trumpet (the daffodil) to a ringlike cup (poet’s Narcissus) and in yellow, white, and pink.⁷

Distribution and Plant Facts

Distribution—There are approximately 80 to 100 wild Narcissus species, which are found in southwestern Europe, North Africa, the Balkan Peninsula, Italy, and France. There are more than 27,000 Narcissus cultivars registered in the International Daffodil Register.⁸

Plant Facts—The daffodil is the national flower of Wales. It also is often used to depict hope and joy and is the symbol of cancer charities in many countries.⁹

The name Narcissus is believed to have originated from Greek mythology. A handsome youth, Narcissus, fell in love with his own reflection, for which the gods punished him by turning him into a flower.¹⁰

Another theory states that Narcissus is derived from the Greek word narkao (to benumb) due to its narcotic properties. When an open wound is subjected to an extract of the bulb, numbness of the entire nervous system is said to occur as well as paralysis of the heart. This narcotic effect led Socrates to refer to the Narcissus plant as the “chaplet of the infernal gods.”¹¹

Narcissus is an important flower in various ethnic rituals. The Greeks often planted daffodils near tombs. In Muslim culture, white is believed to be the symbol of good and purity; Narcissus was one of the most common white-flowered plants found in Muslim graveyards.¹²

Medicinal Qualities and Uses—Narcissus species have been used as medicinal plants for a variety of ailments. For example, Narcissus tazetta contains flavonoids, alkaloids, saponins, tannins, cardiac glycosides, oil, steroids, terpenoids, and anthraquinones that contribute to its antibacterial, antifungal, antiviral, antimalarial, anticancer, antioxidant, dermatologic, cardiovascular, immunomodulatory, and acetylcholinesterase inhibitory effects.¹³ In a study, chloroform extracts from N tazetta bulbs were found to be more active than doxorubicin against hepatocellular and colon cancer cell lines.¹⁴

More than 500 alkaloids have been isolated from the Narcissus genus.¹⁵ In 2001, the US Food and Drug Administration approved one of the alkaloids, galantamine, for the treatment of mild to moderate stages of Alzheimer disease.¹⁶ Galantamine selectively and reversibly inhibits acetylcholinesterase, the enzyme believed responsible for neurodegeneration seen in Alzheimer disease. Plants are the main source of galantamine, despite the ability of pharmaceutical companies to synthesize the compound. Galantamine hydrobromide is sold by prescription (Razadyne [Janssen Pharmaceuticals, Inc]); generic formulations approved by the US Food and Drug Administration have been produced by more than 15 pharmaceutical companies.^17,18

Irritant and Allergen

Sap found in the bulbs and hollow stems of Narcissus contains calcium oxalate crystals, or raphides. The minute, needle-shaped calcium oxalate crystals are believed to be a waste product of cellular metabolism.¹⁹ When the plant structure is compromised by pickers snapping the stalk, the sharp crystals penetrate the skin to cause an irritant contact dermatitis.

Relevant Research—A study used electron microscopy to characterize the structure of raphides from various plants,² though not from Narcissus species; the structure of each raphide was then compared to the degree of irritation it produced. The researchers concluded that more elongated crystals (those containing barbs) produce a greater degree of irritation. Narcissus species are known to cause varying degrees of skin irritation: For example, N tazetta rarely causes skin irritation, whereas N pseudonarcissi (daffodil) tends to cause remarkably more skin irritation.²

Allergic reactions to and strong toxicity from Narcissus species are not well understood. In a study, only 2 alkaloids—homolycorine and masonin—produced a weakly positive reaction in patch tests on sensitized guinea pigs, which correlates with the finding of a different study, in which only 2 of 12 patients whose findings were examined over 14 years had a positive patch test for Narcissus.^20,21

However, IgE-mediated allergies indicative of an allergic response to Narcissus have been reported. A study isolated an allergenic protein, narcin, from bulbs of N tazetta. Narcin is a 13-kDa protein with potent allergenic effects capable of inducing production of proinflammatory cytokines and increasing IgE levels in mononuclear cells in peripheral blood.²²

More research is required to find and understand the compounds responsible for causing an allergic reaction to Narcissus.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.