Environmental Dermatology

What is West Nile virus? How is it contracted, and who can become infected?

West Nile virus (WNV) is a single-stranded RNA virus of the Flaviviridae family and Flavivirus genus, a lineage that also includes the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses.¹ Birds serve as the reservoir hosts of WNV, and mosquitoes acquire the virus during feeding.² West Nile virus then is transmitted to humans primarily by bites from Culex mosquitoes, which are especially prevalent in wooded areas during peak mosquito season (summer through early fall in North America).¹ Mosquitoes also can infect horses; however, humans and horses are dead-end hosts, meaning they do not pass the virus on to other biting mosquitoes.³ There also have been rare reports of transmission of WNV through blood and donation as well as mother-to-baby transmission.²

What is the epidemiology of WNV in the United States?

Since the introduction of WNV to the United States in 1999, it has become an important public health concern, with 48,183 cases and 2163 deaths reported since 1999.^2,3 In 2018, Nebraska had the highest number of cases of WNV (n=251), followed by California (n=217), North Dakota (n=204), Illinois (n=176), and South Dakota (n=169).³ West Nile virus is endemic to all 48 contiguous states and Canada, though the Great Plains region is especially affected by WNV due to several factors, such as a greater percentage of rural land, forests, and irrigated areas.⁴ The Great Plains region also has been thought to be an ecological niche for a more virulent species (Culex tarsalis) compared to other regions in the United States.⁵

The annual incidence of WNV in the United States peaked in 2003 at 9862 cases (up from 62 cases in 1999), then declined gradually until 2008 to 2011, during which the incidence was stable at 700 to 1100 new cases per year. However, there was a resurgence of cases (n=5674) in 2012 that steadied at around 2200 cases annually in subsequent years.⁶ Although there likely are several factors affecting WNV incidence trends in the United States, interannual changes in temperature and precipitation have been described. An increased mean annual temperature (from September through October, the end of peak mosquito season) and an increased temperature in winter months (from January through March, prior to peak mosquito season) have both been associated with an increased incidence of WNV.⁷ An increased temperature is thought to increase population numbers of mosquitoes both by increasing reproductive rates and creating ideal breeding environments via pooled water areas.⁸ Depending on the region, both above average and below average precipitation levels in the United States can increase WNV incidence the following year.^7,9

What are the signs and symptoms of WNV infection?

Up to 80% of those infected with WNV are asymptomatic.³ After an incubation period of roughly 2 to 14 days, the remaining 20% may develop symptoms of West Nile fever (WNF), typically a self-limited illness that consists of 3 to 10 days of nonspecific symptoms such as fever, headache, fatigue, muscle pain and/or weakness, eye pain, gastrointestinal tract upset, and a macular rash that usually presents on the trunk or extremities.^1,3 Less than 1% of patients affected by WNV develop neuroinvasive disease, including meningitis, encephalitis, and/or acute flaccid paralysis.¹⁰ West Nile virus neuroinvasive disease can cause permanent neurologic sequelae such as muscle weakness, confusion, memory loss, and fatigue; it carries a mortality rate of 10% to 30%, which is mainly dependent on older age and immunosuppression status.^1,10

What is the reported spectrum of cutaneous findings in WNV?

Of the roughly 20% of patients infected with WNV that develop WNF, approximately 25% to 50% will develop an associated rash.¹ It most commonly is described as a morbilliform or maculopapular rash located on the chest, back, and arms, usually sparing the palms and soles, though 1 case report noted involvement with these areas (Figure).^11,12 It typically appears 5 days after symptom onset, can be associated with defervescence, and lasts less than a week.^1,13 Pruritus and dysesthesia are sometimes present.¹³ Other rare presentations that have been reported include an ill-defined pseudovesicular rash with erythematous papules on the palms and pink, scaly, psoriasiform papules on the feet and thighs, as well as neuroinvasive WNV leading to purpura fulminans.^14,15 A diffuse, erythematous, petechial rash on the face, neck, trunk, and extremities was reported in a pediatric patient, but there have been no reports of a petechial rash associated with WNV in adult patients.¹⁶ These findings suggest some potential variability in the presentation of the WNV rash.

What role does the presence of rash play diagnostically and prognostically?

The rash of WNV has been implicated as a potential prognostic factor in predicting more favorable outcomes.¹⁷ Using 2002 data from the Illinois Department of Public Health and 2003 data from the Colorado Department of Public Health, Huhn and Dworkin¹⁷ found the age-adjusted risk of encephalitis and death to be decreased in WNV patients with a rash (relative risk, 0.44; 95% CI, 0.21-0.92). The reasons for this are not definitively known, but we hypothesize that the rash may prompt patients to seek earlier medical attention or indicate a more robust immune response. Additionally, a rash in WNV more commonly is seen in younger patients, whereas WNV neuroinvasive disease is more common in older patients, who also tend to have worse outcomes.¹⁰ One study found rash to be the only symptom that demonstrated a significant association with seropositivity (overall risk=6.35; P<.05; 95% CI, 3.75-10.80) by multivariate analysis.¹⁸

How is WNV diagnosed? What are the downsides to WNV testing?

Given that the presenting symptoms of WNV and WNF are nonspecific, it becomes challenging to arrive at the diagnosis based solely on physical examination. As such, the patient’s clinical and epidemiologic history, such as timing, pattern, and appearance of the rash or recent history of mosquito bites, is key to arriving at the correct diagnosis. With clinical suspicion, possible diagnostic tests include an IgM enzyme-linked immunosorbent assay (ELISA) for WNV, a plaque reduction neutralization test (PNRT), and blood polymerase chain reaction (PCR).

An ELISA is a confirmatory test to detect IgM antibodies to WNV in the serum. Because IgM seroconversion typically occurs between days 4 and 10 of symptom onset, there is a high probability of initial false-negative testing within the first 8 days after symptom onset.^19,20 Clinical understanding of this fact is imperative, as an initial negative ELISA does not rule out WNV, and a retest is warranted if clinical suspicion is high. In addition to a high initial false-negative rate with ELISA, there are several other limitations to note. IgM antibodies remain elevated for 1 to 3 months or possibly up to a year in immunocompromised patients.¹ Due to this, false positives may be present if there was a recent prior infection. Enzyme-linked immunosorbent assay may not distinguish from different flaviviruses, including the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses. Seropositivity has been estimated in some states, including 1999 data from New York (2.6%), 2003 data from Nebraska (9.5%), and 2012-2014 data from Connecticut (8.5%).^21-23 Regional variance may be expected, as there also were significant differences in WNV seropositivity between different regions in Nebraska (P<.001).²³

Because ELISA testing for WNV has readily apparent flaws, other tests have been utilized in its diagnosis. The PNRT is the most specific test, and it works by measuring neutralizing antibody titers for different flaviviruses. It has the ability to determine cross-reactivity with other flaviviruses; however, it does not discriminate between a current infection and a prior infection or prior flavivirus vaccine (ie, yellow fever vaccine). Despite this, a positive PNRT can lend credibility to a positive ELISA test and determine specificity for WNV for those with no prior flavivirus exposure.²⁴ According to the Centers for Disease Control and Prevention (CDC), this test can be performed by the CDC or in reference laboratories designated by the CDC.³ Additionally, some state health laboratories may perform PRNTs.

Viral detection with PCR currently is used to screen blood donations and may be beneficial for immunocompromised patients that lack the ability to form a robust antibody response or if a patient presents early, as PCR works best within the first week of symptom onset.¹ Tilley et al²⁵ showed that a combination of PCR and ELISA were able to accurately predict 94.2% of patients (180/191) with documented WNV on a first blood sample compared to 45% and 58.1% for only viral detection or ELISA, respectively. Based on costs from a Midwest academic center, antibody detection tests are around $100 while PCR may range from $500 to $1000 and is only performed in reference laboratories. Although these tests remain in the repertoire for WNV diagnosis, financial stewardship is important.

If there are symptoms of photophobia, phonophobia, nuchal rigidity, loss of consciousness, or marked personality changes, a lumbar puncture for WNV IgM in the cerebrospinal fluid can be performed. As with most viral infections, cerebrospinal fluid findings normally include an elevated protein and lymphocyte count, but neutrophils may be predominantly elevated if the infection is early in its course.²⁶

What are the management options?

To date, there is no curative treatment for WNV, and management is largely supportive. For WNF, over-the-counter pain medications may be helpful to reduce fever and pain. If more severe disease develops, hospitalization for further supportive care may be needed.²⁷ If meningitis or encephalitis is suspected, broad-spectrum antibiotics may need to be started until other common etiologies are ruled out.²⁸

How can you prevent WNV infection?

Disease prevention largely consists of educating the public to avoid heavily wooded areas, especially in areas of high prevalence and during peak months, and to use protective clothing and insect repellant that has been approved by the Environmental Protection Agency.³ Insect repellants approved by the Environmental Protection Agency contain ingredients such as DEET (N, N-diethyl-meta-toluamide), picaridin, IR3535 (ethyl butylacetylaminopropionate), and oil of lemon eucalyptus, which have been proven safe and effective.²⁹ Patients also can protect their homes by using window screens and promptly repairing screens with holes.³

What is the differential diagnosis for WNV?

The differential diagnosis for fever with generalized maculopapular rash broadly ranges from viral etiologies (eg, WNV, Zika, measles), to tick bites (eg, Rocky Mountain spotted fever, ehrlichiosis), to drug-induced rashes. A detailed patient history inquiring on recent sick contacts, travel (WNV in the Midwest, ehrlichiosis in the Southeast), environmental exposures (ticks, mosquitoes), and new medications (typically 7–10 days after starting) is imperative to narrow the differential.³⁰ In addition, the distribution, timing, and clinical characteristics of the rash may aid in diagnosis, along with an appropriately correlated clinical picture. West Nile virus likely will present in the summer in mid central geographic locations and often develops on the trunk and extremities as a blanching, generalized, maculopapular rash around 5 days after symptom onset or with defervescence.¹

What is West Nile virus? How is it contracted, and who can become infected?

West Nile virus (WNV) is a single-stranded RNA virus of the Flaviviridae family and Flavivirus genus, a lineage that also includes the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses.¹ Birds serve as the reservoir hosts of WNV, and mosquitoes acquire the virus during feeding.² West Nile virus then is transmitted to humans primarily by bites from Culex mosquitoes, which are especially prevalent in wooded areas during peak mosquito season (summer through early fall in North America).¹ Mosquitoes also can infect horses; however, humans and horses are dead-end hosts, meaning they do not pass the virus on to other biting mosquitoes.³ There also have been rare reports of transmission of WNV through blood and donation as well as mother-to-baby transmission.²

What is the epidemiology of WNV in the United States?

Since the introduction of WNV to the United States in 1999, it has become an important public health concern, with 48,183 cases and 2163 deaths reported since 1999.^2,3 In 2018, Nebraska had the highest number of cases of WNV (n=251), followed by California (n=217), North Dakota (n=204), Illinois (n=176), and South Dakota (n=169).³ West Nile virus is endemic to all 48 contiguous states and Canada, though the Great Plains region is especially affected by WNV due to several factors, such as a greater percentage of rural land, forests, and irrigated areas.⁴ The Great Plains region also has been thought to be an ecological niche for a more virulent species (Culex tarsalis) compared to other regions in the United States.⁵

The annual incidence of WNV in the United States peaked in 2003 at 9862 cases (up from 62 cases in 1999), then declined gradually until 2008 to 2011, during which the incidence was stable at 700 to 1100 new cases per year. However, there was a resurgence of cases (n=5674) in 2012 that steadied at around 2200 cases annually in subsequent years.⁶ Although there likely are several factors affecting WNV incidence trends in the United States, interannual changes in temperature and precipitation have been described. An increased mean annual temperature (from September through October, the end of peak mosquito season) and an increased temperature in winter months (from January through March, prior to peak mosquito season) have both been associated with an increased incidence of WNV.⁷ An increased temperature is thought to increase population numbers of mosquitoes both by increasing reproductive rates and creating ideal breeding environments via pooled water areas.⁸ Depending on the region, both above average and below average precipitation levels in the United States can increase WNV incidence the following year.^7,9

What are the signs and symptoms of WNV infection?

Up to 80% of those infected with WNV are asymptomatic.³ After an incubation period of roughly 2 to 14 days, the remaining 20% may develop symptoms of West Nile fever (WNF), typically a self-limited illness that consists of 3 to 10 days of nonspecific symptoms such as fever, headache, fatigue, muscle pain and/or weakness, eye pain, gastrointestinal tract upset, and a macular rash that usually presents on the trunk or extremities.^1,3 Less than 1% of patients affected by WNV develop neuroinvasive disease, including meningitis, encephalitis, and/or acute flaccid paralysis.¹⁰ West Nile virus neuroinvasive disease can cause permanent neurologic sequelae such as muscle weakness, confusion, memory loss, and fatigue; it carries a mortality rate of 10% to 30%, which is mainly dependent on older age and immunosuppression status.^1,10

What is the reported spectrum of cutaneous findings in WNV?

Of the roughly 20% of patients infected with WNV that develop WNF, approximately 25% to 50% will develop an associated rash.¹ It most commonly is described as a morbilliform or maculopapular rash located on the chest, back, and arms, usually sparing the palms and soles, though 1 case report noted involvement with these areas (Figure).^11,12 It typically appears 5 days after symptom onset, can be associated with defervescence, and lasts less than a week.^1,13 Pruritus and dysesthesia are sometimes present.¹³ Other rare presentations that have been reported include an ill-defined pseudovesicular rash with erythematous papules on the palms and pink, scaly, psoriasiform papules on the feet and thighs, as well as neuroinvasive WNV leading to purpura fulminans.^14,15 A diffuse, erythematous, petechial rash on the face, neck, trunk, and extremities was reported in a pediatric patient, but there have been no reports of a petechial rash associated with WNV in adult patients.¹⁶ These findings suggest some potential variability in the presentation of the WNV rash.

What role does the presence of rash play diagnostically and prognostically?

The rash of WNV has been implicated as a potential prognostic factor in predicting more favorable outcomes.¹⁷ Using 2002 data from the Illinois Department of Public Health and 2003 data from the Colorado Department of Public Health, Huhn and Dworkin¹⁷ found the age-adjusted risk of encephalitis and death to be decreased in WNV patients with a rash (relative risk, 0.44; 95% CI, 0.21-0.92). The reasons for this are not definitively known, but we hypothesize that the rash may prompt patients to seek earlier medical attention or indicate a more robust immune response. Additionally, a rash in WNV more commonly is seen in younger patients, whereas WNV neuroinvasive disease is more common in older patients, who also tend to have worse outcomes.¹⁰ One study found rash to be the only symptom that demonstrated a significant association with seropositivity (overall risk=6.35; P<.05; 95% CI, 3.75-10.80) by multivariate analysis.¹⁸

How is WNV diagnosed? What are the downsides to WNV testing?

Given that the presenting symptoms of WNV and WNF are nonspecific, it becomes challenging to arrive at the diagnosis based solely on physical examination. As such, the patient’s clinical and epidemiologic history, such as timing, pattern, and appearance of the rash or recent history of mosquito bites, is key to arriving at the correct diagnosis. With clinical suspicion, possible diagnostic tests include an IgM enzyme-linked immunosorbent assay (ELISA) for WNV, a plaque reduction neutralization test (PNRT), and blood polymerase chain reaction (PCR).

An ELISA is a confirmatory test to detect IgM antibodies to WNV in the serum. Because IgM seroconversion typically occurs between days 4 and 10 of symptom onset, there is a high probability of initial false-negative testing within the first 8 days after symptom onset.^19,20 Clinical understanding of this fact is imperative, as an initial negative ELISA does not rule out WNV, and a retest is warranted if clinical suspicion is high. In addition to a high initial false-negative rate with ELISA, there are several other limitations to note. IgM antibodies remain elevated for 1 to 3 months or possibly up to a year in immunocompromised patients.¹ Due to this, false positives may be present if there was a recent prior infection. Enzyme-linked immunosorbent assay may not distinguish from different flaviviruses, including the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses. Seropositivity has been estimated in some states, including 1999 data from New York (2.6%), 2003 data from Nebraska (9.5%), and 2012-2014 data from Connecticut (8.5%).^21-23 Regional variance may be expected, as there also were significant differences in WNV seropositivity between different regions in Nebraska (P<.001).²³

Because ELISA testing for WNV has readily apparent flaws, other tests have been utilized in its diagnosis. The PNRT is the most specific test, and it works by measuring neutralizing antibody titers for different flaviviruses. It has the ability to determine cross-reactivity with other flaviviruses; however, it does not discriminate between a current infection and a prior infection or prior flavivirus vaccine (ie, yellow fever vaccine). Despite this, a positive PNRT can lend credibility to a positive ELISA test and determine specificity for WNV for those with no prior flavivirus exposure.²⁴ According to the Centers for Disease Control and Prevention (CDC), this test can be performed by the CDC or in reference laboratories designated by the CDC.³ Additionally, some state health laboratories may perform PRNTs.

Viral detection with PCR currently is used to screen blood donations and may be beneficial for immunocompromised patients that lack the ability to form a robust antibody response or if a patient presents early, as PCR works best within the first week of symptom onset.¹ Tilley et al²⁵ showed that a combination of PCR and ELISA were able to accurately predict 94.2% of patients (180/191) with documented WNV on a first blood sample compared to 45% and 58.1% for only viral detection or ELISA, respectively. Based on costs from a Midwest academic center, antibody detection tests are around $100 while PCR may range from $500 to $1000 and is only performed in reference laboratories. Although these tests remain in the repertoire for WNV diagnosis, financial stewardship is important.

If there are symptoms of photophobia, phonophobia, nuchal rigidity, loss of consciousness, or marked personality changes, a lumbar puncture for WNV IgM in the cerebrospinal fluid can be performed. As with most viral infections, cerebrospinal fluid findings normally include an elevated protein and lymphocyte count, but neutrophils may be predominantly elevated if the infection is early in its course.²⁶

What are the management options?

To date, there is no curative treatment for WNV, and management is largely supportive. For WNF, over-the-counter pain medications may be helpful to reduce fever and pain. If more severe disease develops, hospitalization for further supportive care may be needed.²⁷ If meningitis or encephalitis is suspected, broad-spectrum antibiotics may need to be started until other common etiologies are ruled out.²⁸

How can you prevent WNV infection?

Disease prevention largely consists of educating the public to avoid heavily wooded areas, especially in areas of high prevalence and during peak months, and to use protective clothing and insect repellant that has been approved by the Environmental Protection Agency.³ Insect repellants approved by the Environmental Protection Agency contain ingredients such as DEET (N, N-diethyl-meta-toluamide), picaridin, IR3535 (ethyl butylacetylaminopropionate), and oil of lemon eucalyptus, which have been proven safe and effective.²⁹ Patients also can protect their homes by using window screens and promptly repairing screens with holes.³

What is the differential diagnosis for WNV?

The differential diagnosis for fever with generalized maculopapular rash broadly ranges from viral etiologies (eg, WNV, Zika, measles), to tick bites (eg, Rocky Mountain spotted fever, ehrlichiosis), to drug-induced rashes. A detailed patient history inquiring on recent sick contacts, travel (WNV in the Midwest, ehrlichiosis in the Southeast), environmental exposures (ticks, mosquitoes), and new medications (typically 7–10 days after starting) is imperative to narrow the differential.³⁰ In addition, the distribution, timing, and clinical characteristics of the rash may aid in diagnosis, along with an appropriately correlated clinical picture. West Nile virus likely will present in the summer in mid central geographic locations and often develops on the trunk and extremities as a blanching, generalized, maculopapular rash around 5 days after symptom onset or with defervescence.¹

What is West Nile virus? How is it contracted, and who can become infected?

West Nile virus (WNV) is a single-stranded RNA virus of the Flaviviridae family and Flavivirus genus, a lineage that also includes the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses.¹ Birds serve as the reservoir hosts of WNV, and mosquitoes acquire the virus during feeding.² West Nile virus then is transmitted to humans primarily by bites from Culex mosquitoes, which are especially prevalent in wooded areas during peak mosquito season (summer through early fall in North America).¹ Mosquitoes also can infect horses; however, humans and horses are dead-end hosts, meaning they do not pass the virus on to other biting mosquitoes.³ There also have been rare reports of transmission of WNV through blood and donation as well as mother-to-baby transmission.²

What is the epidemiology of WNV in the United States?

Since the introduction of WNV to the United States in 1999, it has become an important public health concern, with 48,183 cases and 2163 deaths reported since 1999.^2,3 In 2018, Nebraska had the highest number of cases of WNV (n=251), followed by California (n=217), North Dakota (n=204), Illinois (n=176), and South Dakota (n=169).³ West Nile virus is endemic to all 48 contiguous states and Canada, though the Great Plains region is especially affected by WNV due to several factors, such as a greater percentage of rural land, forests, and irrigated areas.⁴ The Great Plains region also has been thought to be an ecological niche for a more virulent species (Culex tarsalis) compared to other regions in the United States.⁵

The annual incidence of WNV in the United States peaked in 2003 at 9862 cases (up from 62 cases in 1999), then declined gradually until 2008 to 2011, during which the incidence was stable at 700 to 1100 new cases per year. However, there was a resurgence of cases (n=5674) in 2012 that steadied at around 2200 cases annually in subsequent years.⁶ Although there likely are several factors affecting WNV incidence trends in the United States, interannual changes in temperature and precipitation have been described. An increased mean annual temperature (from September through October, the end of peak mosquito season) and an increased temperature in winter months (from January through March, prior to peak mosquito season) have both been associated with an increased incidence of WNV.⁷ An increased temperature is thought to increase population numbers of mosquitoes both by increasing reproductive rates and creating ideal breeding environments via pooled water areas.⁸ Depending on the region, both above average and below average precipitation levels in the United States can increase WNV incidence the following year.^7,9

What are the signs and symptoms of WNV infection?

Up to 80% of those infected with WNV are asymptomatic.³ After an incubation period of roughly 2 to 14 days, the remaining 20% may develop symptoms of West Nile fever (WNF), typically a self-limited illness that consists of 3 to 10 days of nonspecific symptoms such as fever, headache, fatigue, muscle pain and/or weakness, eye pain, gastrointestinal tract upset, and a macular rash that usually presents on the trunk or extremities.^1,3 Less than 1% of patients affected by WNV develop neuroinvasive disease, including meningitis, encephalitis, and/or acute flaccid paralysis.¹⁰ West Nile virus neuroinvasive disease can cause permanent neurologic sequelae such as muscle weakness, confusion, memory loss, and fatigue; it carries a mortality rate of 10% to 30%, which is mainly dependent on older age and immunosuppression status.^1,10

What is the reported spectrum of cutaneous findings in WNV?

Of the roughly 20% of patients infected with WNV that develop WNF, approximately 25% to 50% will develop an associated rash.¹ It most commonly is described as a morbilliform or maculopapular rash located on the chest, back, and arms, usually sparing the palms and soles, though 1 case report noted involvement with these areas (Figure).^11,12 It typically appears 5 days after symptom onset, can be associated with defervescence, and lasts less than a week.^1,13 Pruritus and dysesthesia are sometimes present.¹³ Other rare presentations that have been reported include an ill-defined pseudovesicular rash with erythematous papules on the palms and pink, scaly, psoriasiform papules on the feet and thighs, as well as neuroinvasive WNV leading to purpura fulminans.^14,15 A diffuse, erythematous, petechial rash on the face, neck, trunk, and extremities was reported in a pediatric patient, but there have been no reports of a petechial rash associated with WNV in adult patients.¹⁶ These findings suggest some potential variability in the presentation of the WNV rash.

What role does the presence of rash play diagnostically and prognostically?

The rash of WNV has been implicated as a potential prognostic factor in predicting more favorable outcomes.¹⁷ Using 2002 data from the Illinois Department of Public Health and 2003 data from the Colorado Department of Public Health, Huhn and Dworkin¹⁷ found the age-adjusted risk of encephalitis and death to be decreased in WNV patients with a rash (relative risk, 0.44; 95% CI, 0.21-0.92). The reasons for this are not definitively known, but we hypothesize that the rash may prompt patients to seek earlier medical attention or indicate a more robust immune response. Additionally, a rash in WNV more commonly is seen in younger patients, whereas WNV neuroinvasive disease is more common in older patients, who also tend to have worse outcomes.¹⁰ One study found rash to be the only symptom that demonstrated a significant association with seropositivity (overall risk=6.35; P<.05; 95% CI, 3.75-10.80) by multivariate analysis.¹⁸

How is WNV diagnosed? What are the downsides to WNV testing?

Given that the presenting symptoms of WNV and WNF are nonspecific, it becomes challenging to arrive at the diagnosis based solely on physical examination. As such, the patient’s clinical and epidemiologic history, such as timing, pattern, and appearance of the rash or recent history of mosquito bites, is key to arriving at the correct diagnosis. With clinical suspicion, possible diagnostic tests include an IgM enzyme-linked immunosorbent assay (ELISA) for WNV, a plaque reduction neutralization test (PNRT), and blood polymerase chain reaction (PCR).

An ELISA is a confirmatory test to detect IgM antibodies to WNV in the serum. Because IgM seroconversion typically occurs between days 4 and 10 of symptom onset, there is a high probability of initial false-negative testing within the first 8 days after symptom onset.^19,20 Clinical understanding of this fact is imperative, as an initial negative ELISA does not rule out WNV, and a retest is warranted if clinical suspicion is high. In addition to a high initial false-negative rate with ELISA, there are several other limitations to note. IgM antibodies remain elevated for 1 to 3 months or possibly up to a year in immunocompromised patients.¹ Due to this, false positives may be present if there was a recent prior infection. Enzyme-linked immunosorbent assay may not distinguish from different flaviviruses, including the yellow fever, dengue, Zika, Japanese encephalitis, and Saint Louis encephalitis viruses. Seropositivity has been estimated in some states, including 1999 data from New York (2.6%), 2003 data from Nebraska (9.5%), and 2012-2014 data from Connecticut (8.5%).^21-23 Regional variance may be expected, as there also were significant differences in WNV seropositivity between different regions in Nebraska (P<.001).²³

Because ELISA testing for WNV has readily apparent flaws, other tests have been utilized in its diagnosis. The PNRT is the most specific test, and it works by measuring neutralizing antibody titers for different flaviviruses. It has the ability to determine cross-reactivity with other flaviviruses; however, it does not discriminate between a current infection and a prior infection or prior flavivirus vaccine (ie, yellow fever vaccine). Despite this, a positive PNRT can lend credibility to a positive ELISA test and determine specificity for WNV for those with no prior flavivirus exposure.²⁴ According to the Centers for Disease Control and Prevention (CDC), this test can be performed by the CDC or in reference laboratories designated by the CDC.³ Additionally, some state health laboratories may perform PRNTs.

Viral detection with PCR currently is used to screen blood donations and may be beneficial for immunocompromised patients that lack the ability to form a robust antibody response or if a patient presents early, as PCR works best within the first week of symptom onset.¹ Tilley et al²⁵ showed that a combination of PCR and ELISA were able to accurately predict 94.2% of patients (180/191) with documented WNV on a first blood sample compared to 45% and 58.1% for only viral detection or ELISA, respectively. Based on costs from a Midwest academic center, antibody detection tests are around $100 while PCR may range from $500 to $1000 and is only performed in reference laboratories. Although these tests remain in the repertoire for WNV diagnosis, financial stewardship is important.

If there are symptoms of photophobia, phonophobia, nuchal rigidity, loss of consciousness, or marked personality changes, a lumbar puncture for WNV IgM in the cerebrospinal fluid can be performed. As with most viral infections, cerebrospinal fluid findings normally include an elevated protein and lymphocyte count, but neutrophils may be predominantly elevated if the infection is early in its course.²⁶

What are the management options?

To date, there is no curative treatment for WNV, and management is largely supportive. For WNF, over-the-counter pain medications may be helpful to reduce fever and pain. If more severe disease develops, hospitalization for further supportive care may be needed.²⁷ If meningitis or encephalitis is suspected, broad-spectrum antibiotics may need to be started until other common etiologies are ruled out.²⁸

How can you prevent WNV infection?

Disease prevention largely consists of educating the public to avoid heavily wooded areas, especially in areas of high prevalence and during peak months, and to use protective clothing and insect repellant that has been approved by the Environmental Protection Agency.³ Insect repellants approved by the Environmental Protection Agency contain ingredients such as DEET (N, N-diethyl-meta-toluamide), picaridin, IR3535 (ethyl butylacetylaminopropionate), and oil of lemon eucalyptus, which have been proven safe and effective.²⁹ Patients also can protect their homes by using window screens and promptly repairing screens with holes.³

What is the differential diagnosis for WNV?

The differential diagnosis for fever with generalized maculopapular rash broadly ranges from viral etiologies (eg, WNV, Zika, measles), to tick bites (eg, Rocky Mountain spotted fever, ehrlichiosis), to drug-induced rashes. A detailed patient history inquiring on recent sick contacts, travel (WNV in the Midwest, ehrlichiosis in the Southeast), environmental exposures (ticks, mosquitoes), and new medications (typically 7–10 days after starting) is imperative to narrow the differential.³⁰ In addition, the distribution, timing, and clinical characteristics of the rash may aid in diagnosis, along with an appropriately correlated clinical picture. West Nile virus likely will present in the summer in mid central geographic locations and often develops on the trunk and extremities as a blanching, generalized, maculopapular rash around 5 days after symptom onset or with defervescence.¹

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

The order Lepidoptera (phylum Arthropoda, class Hexapoda) is comprised of moths and butterflies.¹ Lepidopterism refers to a range of adverse medical conditions resulting from contact with these insects, typically during the caterpillar (larval) stage. It involves multiple pathologic mechanisms, including direct toxicity of venom and mechanical irritant effects.² Erucism has been defined as any reaction caused by contact with caterpillars or any reaction limited to the skin caused by contact with caterpillars, butterflies, or moths. Lepidopterism can mean any reaction to caterpillars or moths, referring only to reactions from contact with scales or hairs from adult moths or butterflies, or referring only to cases with systemic signs and symptoms (eg, rhinoconjunctival or asthmatic symptoms, angioedema and anaphylaxis, hemorrhagic diathesis) with or without cutaneous findings, resulting from contact with any lepidopteran source.¹ Strictly speaking, erucism should refer to any reaction from caterpillars and lepidopterism to reactions from moths or butterflies. Because reactions to both larval and adult lepidoptera can cause a variety of either cutaneous and/or systemic symptoms, classifying reactions into erucism or lepidopterism is only of academic interest.¹

We report a documented case of lepidopterism in a patient with acute cutaneous lesions following exposure to an adult-stage black butterfly (Hylesia nigricans).

Case Report

A 21-year-old oil well worker presented with pruritic skin lesions on the right arm and flank of 3 hours’ duration. He reported that a black butterfly had perched on his arm while he was working and left a considerable number of small yellowish hairs on the skin, after which an intense pruritus and skin lesions began to develop. He denied other associated symptoms. Physical examination revealed numerous 1- to 2-mm, nonconfluent, erythematous and edematous papules on the right forearm, arm (Figure 1A), and flank. Some abrasions of the skin due to scratching and crusting were noted (Figure 1B). A skin biopsy from the right arm showed a superficial perivascular dermatitis with a mixed infiltrate of polymorphonuclear predominance with eosinophils (Figure 2A). Importantly, a structure resembling an urticating spicule was identified in the stratum corneum (Figure 2B); spicules are located on the abdomen of arthropods and are associated with an inflammatory response in human skin.

Based on the patient’s history of butterfly exposure, clinical presentation of the lesions, and histopathologic findings demonstrating the presence of the spicules, the diagnosis of lepidopterism was confirmed. The patient was treated with oral antihistamines and topical steroids for 1 week with complete resolution of the lesions.

Comment

Epidemiology of Envenomation
Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, such as dermatitis caused by contact with the skin (erucism or lepidopterism). Caterpillar envenomation is common, but this phenomenon rarely has been studied due to few reported cases, which hinders a complete understanding of the problem.³

The order Lepidoptera comprises 2 suborders: Rhopalocera, with adult specimens that fly during the daytime (butterflies), and Heterocera, which are largely nocturnal (moths). The stages of development include egg, larva (caterpillar), pupa (chrysalis), and adult (imago), constituting a holometabolic life cycle.⁴ Adult butterflies and moths represent the reproductive stage of lepidoptera.

The pathology of lepidopterism is attributed to contact with fluids such as hemolymph and secretions from the spicules, with histamine being identified as the main causative component.³ During the reproductive stage, female insects approach light sources and release clouds of bristles from their abdomens that can penetrate human skin and cause an irritating dermatitis.⁵ Lepidopterism can occur following contact with bristles from insects of the Hylesia genus (Saturniidae family), such as in our patient.^3,6 Epidemic outbreaks have been reported in several countries, mainly Argentina, Brazil, and Venezuela.⁵ The patient was located in Colombia, a country without any reported cases of lepidopterism from the black butterfly (H nigricans). Cutaneous reactions to lepidoptera insects come in many forms, most commonly presenting as a mild stinging reaction with a papular eruption, pruritic urticarial papules and plaques, or scaly erythematous papules and plaques in exposed areas.⁷

Histopathologic Findings
The histology of lepidoptera exposure is nonspecific, typically demonstrating epidermal edema, superficial perivascular lymphocytic infiltrate, and eosinophils. Epidermal necrosis and vasculitis rarely are seen. Embedded spines from Hylesia insects have been described.⁷ The histopathologic examination generally reveals a foreign body reaction in addition to granulomas.³

Therapy
The use of oral antihistamines is indicated for the control of pruritus, and topical treatment with cold compresses, baths, and corticosteroid creams is recommended.^3,8,9

Conclusion

We report the case of a patient with lepidopterism, a rare entity confirmed histologically with documentation of a spicule in the stratum corneum in the patient’s biopsy. Changes due to urbanization and industrialization have a closer relationship with various animal species that are pathogenic to humans; therefore, we encourage dermatologists to be aware of these diseases.

The order Lepidoptera (phylum Arthropoda, class Hexapoda) is comprised of moths and butterflies.¹ Lepidopterism refers to a range of adverse medical conditions resulting from contact with these insects, typically during the caterpillar (larval) stage. It involves multiple pathologic mechanisms, including direct toxicity of venom and mechanical irritant effects.² Erucism has been defined as any reaction caused by contact with caterpillars or any reaction limited to the skin caused by contact with caterpillars, butterflies, or moths. Lepidopterism can mean any reaction to caterpillars or moths, referring only to reactions from contact with scales or hairs from adult moths or butterflies, or referring only to cases with systemic signs and symptoms (eg, rhinoconjunctival or asthmatic symptoms, angioedema and anaphylaxis, hemorrhagic diathesis) with or without cutaneous findings, resulting from contact with any lepidopteran source.¹ Strictly speaking, erucism should refer to any reaction from caterpillars and lepidopterism to reactions from moths or butterflies. Because reactions to both larval and adult lepidoptera can cause a variety of either cutaneous and/or systemic symptoms, classifying reactions into erucism or lepidopterism is only of academic interest.¹

We report a documented case of lepidopterism in a patient with acute cutaneous lesions following exposure to an adult-stage black butterfly (Hylesia nigricans).

Case Report

A 21-year-old oil well worker presented with pruritic skin lesions on the right arm and flank of 3 hours’ duration. He reported that a black butterfly had perched on his arm while he was working and left a considerable number of small yellowish hairs on the skin, after which an intense pruritus and skin lesions began to develop. He denied other associated symptoms. Physical examination revealed numerous 1- to 2-mm, nonconfluent, erythematous and edematous papules on the right forearm, arm (Figure 1A), and flank. Some abrasions of the skin due to scratching and crusting were noted (Figure 1B). A skin biopsy from the right arm showed a superficial perivascular dermatitis with a mixed infiltrate of polymorphonuclear predominance with eosinophils (Figure 2A). Importantly, a structure resembling an urticating spicule was identified in the stratum corneum (Figure 2B); spicules are located on the abdomen of arthropods and are associated with an inflammatory response in human skin.

Based on the patient’s history of butterfly exposure, clinical presentation of the lesions, and histopathologic findings demonstrating the presence of the spicules, the diagnosis of lepidopterism was confirmed. The patient was treated with oral antihistamines and topical steroids for 1 week with complete resolution of the lesions.

Comment

Epidemiology of Envenomation
Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, such as dermatitis caused by contact with the skin (erucism or lepidopterism). Caterpillar envenomation is common, but this phenomenon rarely has been studied due to few reported cases, which hinders a complete understanding of the problem.³

The order Lepidoptera comprises 2 suborders: Rhopalocera, with adult specimens that fly during the daytime (butterflies), and Heterocera, which are largely nocturnal (moths). The stages of development include egg, larva (caterpillar), pupa (chrysalis), and adult (imago), constituting a holometabolic life cycle.⁴ Adult butterflies and moths represent the reproductive stage of lepidoptera.

The pathology of lepidopterism is attributed to contact with fluids such as hemolymph and secretions from the spicules, with histamine being identified as the main causative component.³ During the reproductive stage, female insects approach light sources and release clouds of bristles from their abdomens that can penetrate human skin and cause an irritating dermatitis.⁵ Lepidopterism can occur following contact with bristles from insects of the Hylesia genus (Saturniidae family), such as in our patient.^3,6 Epidemic outbreaks have been reported in several countries, mainly Argentina, Brazil, and Venezuela.⁵ The patient was located in Colombia, a country without any reported cases of lepidopterism from the black butterfly (H nigricans). Cutaneous reactions to lepidoptera insects come in many forms, most commonly presenting as a mild stinging reaction with a papular eruption, pruritic urticarial papules and plaques, or scaly erythematous papules and plaques in exposed areas.⁷

Histopathologic Findings
The histology of lepidoptera exposure is nonspecific, typically demonstrating epidermal edema, superficial perivascular lymphocytic infiltrate, and eosinophils. Epidermal necrosis and vasculitis rarely are seen. Embedded spines from Hylesia insects have been described.⁷ The histopathologic examination generally reveals a foreign body reaction in addition to granulomas.³

Therapy
The use of oral antihistamines is indicated for the control of pruritus, and topical treatment with cold compresses, baths, and corticosteroid creams is recommended.^3,8,9

Conclusion

We report the case of a patient with lepidopterism, a rare entity confirmed histologically with documentation of a spicule in the stratum corneum in the patient’s biopsy. Changes due to urbanization and industrialization have a closer relationship with various animal species that are pathogenic to humans; therefore, we encourage dermatologists to be aware of these diseases.

The order Lepidoptera (phylum Arthropoda, class Hexapoda) is comprised of moths and butterflies.¹ Lepidopterism refers to a range of adverse medical conditions resulting from contact with these insects, typically during the caterpillar (larval) stage. It involves multiple pathologic mechanisms, including direct toxicity of venom and mechanical irritant effects.² Erucism has been defined as any reaction caused by contact with caterpillars or any reaction limited to the skin caused by contact with caterpillars, butterflies, or moths. Lepidopterism can mean any reaction to caterpillars or moths, referring only to reactions from contact with scales or hairs from adult moths or butterflies, or referring only to cases with systemic signs and symptoms (eg, rhinoconjunctival or asthmatic symptoms, angioedema and anaphylaxis, hemorrhagic diathesis) with or without cutaneous findings, resulting from contact with any lepidopteran source.¹ Strictly speaking, erucism should refer to any reaction from caterpillars and lepidopterism to reactions from moths or butterflies. Because reactions to both larval and adult lepidoptera can cause a variety of either cutaneous and/or systemic symptoms, classifying reactions into erucism or lepidopterism is only of academic interest.¹

We report a documented case of lepidopterism in a patient with acute cutaneous lesions following exposure to an adult-stage black butterfly (Hylesia nigricans).

Case Report

A 21-year-old oil well worker presented with pruritic skin lesions on the right arm and flank of 3 hours’ duration. He reported that a black butterfly had perched on his arm while he was working and left a considerable number of small yellowish hairs on the skin, after which an intense pruritus and skin lesions began to develop. He denied other associated symptoms. Physical examination revealed numerous 1- to 2-mm, nonconfluent, erythematous and edematous papules on the right forearm, arm (Figure 1A), and flank. Some abrasions of the skin due to scratching and crusting were noted (Figure 1B). A skin biopsy from the right arm showed a superficial perivascular dermatitis with a mixed infiltrate of polymorphonuclear predominance with eosinophils (Figure 2A). Importantly, a structure resembling an urticating spicule was identified in the stratum corneum (Figure 2B); spicules are located on the abdomen of arthropods and are associated with an inflammatory response in human skin.

Based on the patient’s history of butterfly exposure, clinical presentation of the lesions, and histopathologic findings demonstrating the presence of the spicules, the diagnosis of lepidopterism was confirmed. The patient was treated with oral antihistamines and topical steroids for 1 week with complete resolution of the lesions.

Comment

Epidemiology of Envenomation
Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, such as dermatitis caused by contact with the skin (erucism or lepidopterism). Caterpillar envenomation is common, but this phenomenon rarely has been studied due to few reported cases, which hinders a complete understanding of the problem.³

The order Lepidoptera comprises 2 suborders: Rhopalocera, with adult specimens that fly during the daytime (butterflies), and Heterocera, which are largely nocturnal (moths). The stages of development include egg, larva (caterpillar), pupa (chrysalis), and adult (imago), constituting a holometabolic life cycle.⁴ Adult butterflies and moths represent the reproductive stage of lepidoptera.

The pathology of lepidopterism is attributed to contact with fluids such as hemolymph and secretions from the spicules, with histamine being identified as the main causative component.³ During the reproductive stage, female insects approach light sources and release clouds of bristles from their abdomens that can penetrate human skin and cause an irritating dermatitis.⁵ Lepidopterism can occur following contact with bristles from insects of the Hylesia genus (Saturniidae family), such as in our patient.^3,6 Epidemic outbreaks have been reported in several countries, mainly Argentina, Brazil, and Venezuela.⁵ The patient was located in Colombia, a country without any reported cases of lepidopterism from the black butterfly (H nigricans). Cutaneous reactions to lepidoptera insects come in many forms, most commonly presenting as a mild stinging reaction with a papular eruption, pruritic urticarial papules and plaques, or scaly erythematous papules and plaques in exposed areas.⁷

Histopathologic Findings
The histology of lepidoptera exposure is nonspecific, typically demonstrating epidermal edema, superficial perivascular lymphocytic infiltrate, and eosinophils. Epidermal necrosis and vasculitis rarely are seen. Embedded spines from Hylesia insects have been described.⁷ The histopathologic examination generally reveals a foreign body reaction in addition to granulomas.³

Therapy
The use of oral antihistamines is indicated for the control of pruritus, and topical treatment with cold compresses, baths, and corticosteroid creams is recommended.^3,8,9

Conclusion

We report the case of a patient with lepidopterism, a rare entity confirmed histologically with documentation of a spicule in the stratum corneum in the patient’s biopsy. Changes due to urbanization and industrialization have a closer relationship with various animal species that are pathogenic to humans; therefore, we encourage dermatologists to be aware of these diseases.

Sponges are among the oldest animals on earth, appearing more than 640 million years ago before the Cambrian explosion, a period when most major animal phyla appeared in the fossil records.¹ More than 10,000 species of sponges have been identified worldwide and are distributed from polar to tropical regions in both marine (Figure 1) and freshwater (Figure 2) environments. They inhabit both shallow waters as well as depths of more than 2800 m, with shallower sponges tending to be more vibrantly colored than their deeper counterparts. The wide-ranging habitats of sponges have led to size variations from as small as 0.05 mm to more than 3 m in height.² Their taxonomic phylum, Porifera (meaning pore bearers), is derived from the millions of pores lining the surface of the sponge that are used to filter planktonic organisms.³ Flagellated epithelioid cells called choanocytes line the internal chambers of sponges, creating a water current that promotes filter feeding as well as nutrient absorption across their microvilli.⁴ The body walls of many sponges consist of a collagenous skeleton made up of spongin and spicules of silicon dioxide (silica) or calcium carbonate embedded in the spongin connective tissue matrix.⁵ Bath sponges lack silica spicules.

Sponges have been used in medicine for centuries. The first use in Western culture was recorded in 405 bce in The Frogs, a comedy by Aristophanes in which a sponge was placed on a character’s heart following a syncopal episode. Additionally, in many Hippocratic writings, the use of sponges is outlined in the treatment of a variety of ailments. Similarly, the ancient Chinese and Greeks used burnt sponge and seaweed as a source of iodine to treat goiters.^6,7 Modern research focuses on the use of sponge metabolites for their antineoplastic, antimicrobial, and anti-inflammatory effects.⁸ Identification of spongouridine and spongothymidine from the sponge Tectitethya crypta led to the development of cytarabine and gemcitabine⁸ as well as the discovery of the antiviral agent vidarabine.⁹ The monoclonal antibody assay for the detection of shellfish poisoning was prepared using the sponge Halichondria okadai.¹⁰

Mechanisms and Symptoms of Injury

Bathing sponges (silk sponges) derived from Spongia officinalis are harmless. Other sponges can exert their damaging effects through a variety of mechanisms that lead to dermatologic manifestations (eTable). Some species of sponges produce and secrete toxic metabolites (eg, crinotoxins) onto the body surface or into the surrounding water. They also are capable of synthesizing a mucous slime that can be irritating to human skin. Direct trauma also can be caused by fragments of the silica or calcium carbonate sponge skeleton penetrating the skin. Stinging members of the phylum Cnidaria can colonize the sponge, leading to injury when a human handles the sponge.^25-27

Sponge dermatitis can be divided into 2 major categories: an initial pruritic dermatitis (Figure 3) that occurs within 20 minutes to a few hours after contact and a delayed irritant dermatitis caused by penetration of the spicules and chemical agents into skin.²⁸ Importantly, different species can lead to varying manifestations.

Management

Treatment should consist of an initial decontamination; the skin should be dried, and adhesive tape or rubber cement should be utilized to remove any spicules embedded in the skin. Diluted vinegar soaks should be initiated for 10 to 30 minutes on the affected area(s) 3 or 4 times daily.¹⁹ The initial decontamination should occur immediately, as delay may lead to persistent purulent bullae that may take months to heal. Topical steroids may be used following the initial decontamination to help relieve inflammation. Antihistamines and nonsteroidal anti-inflammatory drugs may be used to alleviate pruritus and pain, respectively. Severe cases may require systemic glucocorticoids. Additionally, immunization status against tetanus toxoid should be assessed.³⁵ In the event of an anaphylactic reaction, it is important to maintain a patent airway and normalized blood pressure through the use of intramuscular epinephrine.³⁶ Frequent follow-up is warranted, as serious secondary infections can develop.³⁷ Patients also should be counseled on the potential for delayed dermatologic reactions, including erythema multiforme. Contact between humans and coastal environments has been increasing in the last few decades; therefore, an increase in contact with sponges is to be expected.²²

Sponges are among the oldest animals on earth, appearing more than 640 million years ago before the Cambrian explosion, a period when most major animal phyla appeared in the fossil records.¹ More than 10,000 species of sponges have been identified worldwide and are distributed from polar to tropical regions in both marine (Figure 1) and freshwater (Figure 2) environments. They inhabit both shallow waters as well as depths of more than 2800 m, with shallower sponges tending to be more vibrantly colored than their deeper counterparts. The wide-ranging habitats of sponges have led to size variations from as small as 0.05 mm to more than 3 m in height.² Their taxonomic phylum, Porifera (meaning pore bearers), is derived from the millions of pores lining the surface of the sponge that are used to filter planktonic organisms.³ Flagellated epithelioid cells called choanocytes line the internal chambers of sponges, creating a water current that promotes filter feeding as well as nutrient absorption across their microvilli.⁴ The body walls of many sponges consist of a collagenous skeleton made up of spongin and spicules of silicon dioxide (silica) or calcium carbonate embedded in the spongin connective tissue matrix.⁵ Bath sponges lack silica spicules.

Sponges have been used in medicine for centuries. The first use in Western culture was recorded in 405 bce in The Frogs, a comedy by Aristophanes in which a sponge was placed on a character’s heart following a syncopal episode. Additionally, in many Hippocratic writings, the use of sponges is outlined in the treatment of a variety of ailments. Similarly, the ancient Chinese and Greeks used burnt sponge and seaweed as a source of iodine to treat goiters.^6,7 Modern research focuses on the use of sponge metabolites for their antineoplastic, antimicrobial, and anti-inflammatory effects.⁸ Identification of spongouridine and spongothymidine from the sponge Tectitethya crypta led to the development of cytarabine and gemcitabine⁸ as well as the discovery of the antiviral agent vidarabine.⁹ The monoclonal antibody assay for the detection of shellfish poisoning was prepared using the sponge Halichondria okadai.¹⁰

Mechanisms and Symptoms of Injury

Bathing sponges (silk sponges) derived from Spongia officinalis are harmless. Other sponges can exert their damaging effects through a variety of mechanisms that lead to dermatologic manifestations (eTable). Some species of sponges produce and secrete toxic metabolites (eg, crinotoxins) onto the body surface or into the surrounding water. They also are capable of synthesizing a mucous slime that can be irritating to human skin. Direct trauma also can be caused by fragments of the silica or calcium carbonate sponge skeleton penetrating the skin. Stinging members of the phylum Cnidaria can colonize the sponge, leading to injury when a human handles the sponge.^25-27

Sponge dermatitis can be divided into 2 major categories: an initial pruritic dermatitis (Figure 3) that occurs within 20 minutes to a few hours after contact and a delayed irritant dermatitis caused by penetration of the spicules and chemical agents into skin.²⁸ Importantly, different species can lead to varying manifestations.

Management

Treatment should consist of an initial decontamination; the skin should be dried, and adhesive tape or rubber cement should be utilized to remove any spicules embedded in the skin. Diluted vinegar soaks should be initiated for 10 to 30 minutes on the affected area(s) 3 or 4 times daily.¹⁹ The initial decontamination should occur immediately, as delay may lead to persistent purulent bullae that may take months to heal. Topical steroids may be used following the initial decontamination to help relieve inflammation. Antihistamines and nonsteroidal anti-inflammatory drugs may be used to alleviate pruritus and pain, respectively. Severe cases may require systemic glucocorticoids. Additionally, immunization status against tetanus toxoid should be assessed.³⁵ In the event of an anaphylactic reaction, it is important to maintain a patent airway and normalized blood pressure through the use of intramuscular epinephrine.³⁶ Frequent follow-up is warranted, as serious secondary infections can develop.³⁷ Patients also should be counseled on the potential for delayed dermatologic reactions, including erythema multiforme. Contact between humans and coastal environments has been increasing in the last few decades; therefore, an increase in contact with sponges is to be expected.²²

Sponges are among the oldest animals on earth, appearing more than 640 million years ago before the Cambrian explosion, a period when most major animal phyla appeared in the fossil records.¹ More than 10,000 species of sponges have been identified worldwide and are distributed from polar to tropical regions in both marine (Figure 1) and freshwater (Figure 2) environments. They inhabit both shallow waters as well as depths of more than 2800 m, with shallower sponges tending to be more vibrantly colored than their deeper counterparts. The wide-ranging habitats of sponges have led to size variations from as small as 0.05 mm to more than 3 m in height.² Their taxonomic phylum, Porifera (meaning pore bearers), is derived from the millions of pores lining the surface of the sponge that are used to filter planktonic organisms.³ Flagellated epithelioid cells called choanocytes line the internal chambers of sponges, creating a water current that promotes filter feeding as well as nutrient absorption across their microvilli.⁴ The body walls of many sponges consist of a collagenous skeleton made up of spongin and spicules of silicon dioxide (silica) or calcium carbonate embedded in the spongin connective tissue matrix.⁵ Bath sponges lack silica spicules.

Sponges have been used in medicine for centuries. The first use in Western culture was recorded in 405 bce in The Frogs, a comedy by Aristophanes in which a sponge was placed on a character’s heart following a syncopal episode. Additionally, in many Hippocratic writings, the use of sponges is outlined in the treatment of a variety of ailments. Similarly, the ancient Chinese and Greeks used burnt sponge and seaweed as a source of iodine to treat goiters.^6,7 Modern research focuses on the use of sponge metabolites for their antineoplastic, antimicrobial, and anti-inflammatory effects.⁸ Identification of spongouridine and spongothymidine from the sponge Tectitethya crypta led to the development of cytarabine and gemcitabine⁸ as well as the discovery of the antiviral agent vidarabine.⁹ The monoclonal antibody assay for the detection of shellfish poisoning was prepared using the sponge Halichondria okadai.¹⁰

Mechanisms and Symptoms of Injury

Bathing sponges (silk sponges) derived from Spongia officinalis are harmless. Other sponges can exert their damaging effects through a variety of mechanisms that lead to dermatologic manifestations (eTable). Some species of sponges produce and secrete toxic metabolites (eg, crinotoxins) onto the body surface or into the surrounding water. They also are capable of synthesizing a mucous slime that can be irritating to human skin. Direct trauma also can be caused by fragments of the silica or calcium carbonate sponge skeleton penetrating the skin. Stinging members of the phylum Cnidaria can colonize the sponge, leading to injury when a human handles the sponge.^25-27

Sponge dermatitis can be divided into 2 major categories: an initial pruritic dermatitis (Figure 3) that occurs within 20 minutes to a few hours after contact and a delayed irritant dermatitis caused by penetration of the spicules and chemical agents into skin.²⁸ Importantly, different species can lead to varying manifestations.

Management

Treatment should consist of an initial decontamination; the skin should be dried, and adhesive tape or rubber cement should be utilized to remove any spicules embedded in the skin. Diluted vinegar soaks should be initiated for 10 to 30 minutes on the affected area(s) 3 or 4 times daily.¹⁹ The initial decontamination should occur immediately, as delay may lead to persistent purulent bullae that may take months to heal. Topical steroids may be used following the initial decontamination to help relieve inflammation. Antihistamines and nonsteroidal anti-inflammatory drugs may be used to alleviate pruritus and pain, respectively. Severe cases may require systemic glucocorticoids. Additionally, immunization status against tetanus toxoid should be assessed.³⁵ In the event of an anaphylactic reaction, it is important to maintain a patent airway and normalized blood pressure through the use of intramuscular epinephrine.³⁶ Frequent follow-up is warranted, as serious secondary infections can develop.³⁷ Patients also should be counseled on the potential for delayed dermatologic reactions, including erythema multiforme. Contact between humans and coastal environments has been increasing in the last few decades; therefore, an increase in contact with sponges is to be expected.²²

Characteristics

The ubiquitous human flea, Pulex irritans, is a hematophagous wingless ectoparasite in the order Siphonaptera (wingless siphon) that survives by consuming the blood of its mammalian and avian hosts. Due to diseases such as the bubonic plague, fleas have claimed more victims than all the wars ever fought; in the 14th century, the Black Death caused more than 200 million deaths. Fleas fossilized in amber have been found to be 200 million years old and closely resemble the modern human flea, demonstrating the resilience of the species.

The adult human flea is a small, reddish brown, laterally compressed, wingless insect that is approximately 2- to 3.5-mm long (females, 2.5–3.5 mm; males, 2–2.5 mm) and enclosed by a tough cuticle. Compared to the dog flea (Ctenocephalides canis) and cat flea (Ctenocephalides felis), P irritans has no combs or ctenidia (Figure 1). Fleas have large powerful hind legs enabling them to jump horizontally or vertically 200 times their body length (equivalent to a 6-foot human jumping 1200 feet) using stored muscle energy in a pad on the hind legs composed of the elastic protein resilin.¹ They feed off a wide variety of hosts, including humans, pigs, cats, dogs, goats, sheep, cattle, chickens, owls, foxes, rabbits, mice, and feral cats. The flea’s mouthparts are highly specialized for piercing the skin and sucking its blood meal via direct capillary cannulation.

Life Cycle

There are 4 stages of the flea life cycle: egg, larva, pupa, and adult. Most adult flea species mate on the host; the female will lay an average of 4 to 8 small white eggs on the host after each blood meal, laying more than 400 eggs during her lifetime. The eggs then drop from the host and hatch in approximately 4 to 6 days to become larvae. The active larvae feed on available organic matter in their environment, such as their parents’ feces and detritus, while undergoing 3 molts within 1 week to several months.² The larva then spins a silken cocoon from modified salivary glands to form the pupa. In favorable conditions, the pupa lasts only a few weeks; however, it can last for a year or more in unfavorable conditions. Triggers for emergence of the adult flea from the pupa include high humidity, warm temperatures, increased levels of carbon dioxide, and vibrations including sound. An adult P irritans flea can live for a few weeks to more than 1.5 years in favorable conditions of lower air temperature, high relative humidity, and access to a host.³

Related Diseases

Pulex irritans can be a vector for several human diseases. Yersinia pestis is a gram-negative bacteria that causes plague, a highly virulent disease that killed millions of people during its 3 largest human pandemics. The black rat (Rattus rattus) and the oriental rat flea (Xenopsylla cheopis) have been implicated as initial vectors; however, transmission may be human-to-human with pneumonic plague, and septicemic plague may be spread via Pulex fleas or body lice.^4,5 In 1971, Y pestis was isolated from P irritans on a dog in the home of a plague patient in Kayenta, Arizona.⁶Yersinia pestis bacterial DNA also was extracted from P irritans during a plague outbreak in Madagascar in 2014⁷ and was implicated in epidemiologic studies of plague in Tanzania from 1986 to 2004, suggesting it also plays a role in endemic disease.⁸

Bartonellosis is an emerging disease caused by different species of the gram-negative intracellular bacteria of the genus Bartonella transmitted by lice, ticks, and fleas. Bartonella quintana causes trench fever primarily transmitted by the human body louse, Pediculus humanus corporis, and resulted in more than 1 million cases during World War I. Trench fever is characterized by headache, fever, dizziness, and shin pain that lasts 1 to 3 days and recurs in cycles every 4 to 6 days. Other clinical manifestations of B quintana include chronic bacteremia, endocarditis, lymphadenopathy, and bacillary angiomatosis.⁹Bartonella henselae causes cat scratch fever, characterized by lymphadenopathy, fever, headache, joint pain, and lethargy from infected cat scratches or the bite of an infected flea. Bartonella rochalimae also has been found to cause a trench fever–like bacteremia.¹⁰Bartonella species have been found in P irritans, and the flea is implicated as a vector of bartonellosis in humans.^11-15

Rickettsioses are worldwide diseases caused by the gram-negative intracellular bacteria of the genus Rickettsia transmitted to humans via hematophagous arthropods. The rickettsiae traditionally have been classified into the spotted fever or typhus groups. The spotted fever group (ie, Rocky Mountain spotted fever, Mediterranean spotted fever) is transmitted via ticks. The typhus group is transmitted via lice (epidemic typhus) and fleas (endemic or murine typhus). Murine typhus can be caused by Rickettsia typhi in warm coastal areas around the world where the main mammal reservoir is the rat and the rat flea vector X cheopis. Clinical signs of infection are abrupt onset of fever, headaches, myalgia, malaise, and chills, with a truncal maculopapular rash progressing peripherally several days after the initial clinical signs. Rash is present in up to 50% of cases.¹⁶Rickettsia felis is an emerging flea-borne pathogen causing an acute febrile illness usually transmitted via the cat flea C felis.¹⁷Rickettsia species DNA have been found to be present in P irritans from dogs¹⁸ and livestock¹⁹ and pose a risk for causing rickettsioses in humans.

Environmental Treatment and Prevention

Flea bites present as intense, pruritic, urticarial to vesicular papules that usually are located on the lower extremities but also can be present on exposed areas of the upper extremities and hands (Figure 2). Human fleas infest clothing, and bites can be widespread. Topical antipruritics and corticosteroids can be used for controlling itch and the intense cutaneous inflammatory response. The flea host should be identified in areas of the home, school, farm, work, or local environment. House pets should be examined and treated by a veterinarian. The pet’s bedding should be washed and dried at high temperatures, and carpets and floors should be routinely vacuumed or cleaned to remove eggs, larvae, flea feces, and/or pupae. The killing of adult fleas with insecticidal products (eg, imidacloprid, fipronil, spinosad, selamectin, lufenuron, ivermectin) is the primary method of flea control. Use of insect growth regulators such as pyriproxyfen inhibits adult reproduction and blocks the organogenesis of immature larval stages via hormonal or enzymatic actions.²⁰ The combination of an insecticide and an insect growth regulator appears to be most effective in their synergistic actions against adult fleas and larvae. There have been reports of insecticidal resistance in the flea population, especially with pyrethroids.^21,22 A professional exterminator and veterinarian should be consulted. In recalcitrant cases, evaluation for other wild mammals or birds should be performed in unoccupied areas of the home such as the attic, crawl spaces, and basements, as well as inside walls.

Conclusion

The human flea, P irritans, is an important vector in the transmission of human diseases such as the bubonic plague, bartonellosis, and rickettsioses. Flea bites present as intensely pruritic, urticarial to vesicular papules that most commonly present on the lower extremities. Flea bites can be treated with topical steroids, and fleas can be controlled by a combination of insecticidal products and insect growth regulators.

Characteristics

The ubiquitous human flea, Pulex irritans, is a hematophagous wingless ectoparasite in the order Siphonaptera (wingless siphon) that survives by consuming the blood of its mammalian and avian hosts. Due to diseases such as the bubonic plague, fleas have claimed more victims than all the wars ever fought; in the 14th century, the Black Death caused more than 200 million deaths. Fleas fossilized in amber have been found to be 200 million years old and closely resemble the modern human flea, demonstrating the resilience of the species.

The adult human flea is a small, reddish brown, laterally compressed, wingless insect that is approximately 2- to 3.5-mm long (females, 2.5–3.5 mm; males, 2–2.5 mm) and enclosed by a tough cuticle. Compared to the dog flea (Ctenocephalides canis) and cat flea (Ctenocephalides felis), P irritans has no combs or ctenidia (Figure 1). Fleas have large powerful hind legs enabling them to jump horizontally or vertically 200 times their body length (equivalent to a 6-foot human jumping 1200 feet) using stored muscle energy in a pad on the hind legs composed of the elastic protein resilin.¹ They feed off a wide variety of hosts, including humans, pigs, cats, dogs, goats, sheep, cattle, chickens, owls, foxes, rabbits, mice, and feral cats. The flea’s mouthparts are highly specialized for piercing the skin and sucking its blood meal via direct capillary cannulation.

Life Cycle

There are 4 stages of the flea life cycle: egg, larva, pupa, and adult. Most adult flea species mate on the host; the female will lay an average of 4 to 8 small white eggs on the host after each blood meal, laying more than 400 eggs during her lifetime. The eggs then drop from the host and hatch in approximately 4 to 6 days to become larvae. The active larvae feed on available organic matter in their environment, such as their parents’ feces and detritus, while undergoing 3 molts within 1 week to several months.² The larva then spins a silken cocoon from modified salivary glands to form the pupa. In favorable conditions, the pupa lasts only a few weeks; however, it can last for a year or more in unfavorable conditions. Triggers for emergence of the adult flea from the pupa include high humidity, warm temperatures, increased levels of carbon dioxide, and vibrations including sound. An adult P irritans flea can live for a few weeks to more than 1.5 years in favorable conditions of lower air temperature, high relative humidity, and access to a host.³

Related Diseases

Pulex irritans can be a vector for several human diseases. Yersinia pestis is a gram-negative bacteria that causes plague, a highly virulent disease that killed millions of people during its 3 largest human pandemics. The black rat (Rattus rattus) and the oriental rat flea (Xenopsylla cheopis) have been implicated as initial vectors; however, transmission may be human-to-human with pneumonic plague, and septicemic plague may be spread via Pulex fleas or body lice.^4,5 In 1971, Y pestis was isolated from P irritans on a dog in the home of a plague patient in Kayenta, Arizona.⁶Yersinia pestis bacterial DNA also was extracted from P irritans during a plague outbreak in Madagascar in 2014⁷ and was implicated in epidemiologic studies of plague in Tanzania from 1986 to 2004, suggesting it also plays a role in endemic disease.⁸

Bartonellosis is an emerging disease caused by different species of the gram-negative intracellular bacteria of the genus Bartonella transmitted by lice, ticks, and fleas. Bartonella quintana causes trench fever primarily transmitted by the human body louse, Pediculus humanus corporis, and resulted in more than 1 million cases during World War I. Trench fever is characterized by headache, fever, dizziness, and shin pain that lasts 1 to 3 days and recurs in cycles every 4 to 6 days. Other clinical manifestations of B quintana include chronic bacteremia, endocarditis, lymphadenopathy, and bacillary angiomatosis.⁹Bartonella henselae causes cat scratch fever, characterized by lymphadenopathy, fever, headache, joint pain, and lethargy from infected cat scratches or the bite of an infected flea. Bartonella rochalimae also has been found to cause a trench fever–like bacteremia.¹⁰Bartonella species have been found in P irritans, and the flea is implicated as a vector of bartonellosis in humans.^11-15

Rickettsioses are worldwide diseases caused by the gram-negative intracellular bacteria of the genus Rickettsia transmitted to humans via hematophagous arthropods. The rickettsiae traditionally have been classified into the spotted fever or typhus groups. The spotted fever group (ie, Rocky Mountain spotted fever, Mediterranean spotted fever) is transmitted via ticks. The typhus group is transmitted via lice (epidemic typhus) and fleas (endemic or murine typhus). Murine typhus can be caused by Rickettsia typhi in warm coastal areas around the world where the main mammal reservoir is the rat and the rat flea vector X cheopis. Clinical signs of infection are abrupt onset of fever, headaches, myalgia, malaise, and chills, with a truncal maculopapular rash progressing peripherally several days after the initial clinical signs. Rash is present in up to 50% of cases.¹⁶Rickettsia felis is an emerging flea-borne pathogen causing an acute febrile illness usually transmitted via the cat flea C felis.¹⁷Rickettsia species DNA have been found to be present in P irritans from dogs¹⁸ and livestock¹⁹ and pose a risk for causing rickettsioses in humans.

Environmental Treatment and Prevention

Flea bites present as intense, pruritic, urticarial to vesicular papules that usually are located on the lower extremities but also can be present on exposed areas of the upper extremities and hands (Figure 2). Human fleas infest clothing, and bites can be widespread. Topical antipruritics and corticosteroids can be used for controlling itch and the intense cutaneous inflammatory response. The flea host should be identified in areas of the home, school, farm, work, or local environment. House pets should be examined and treated by a veterinarian. The pet’s bedding should be washed and dried at high temperatures, and carpets and floors should be routinely vacuumed or cleaned to remove eggs, larvae, flea feces, and/or pupae. The killing of adult fleas with insecticidal products (eg, imidacloprid, fipronil, spinosad, selamectin, lufenuron, ivermectin) is the primary method of flea control. Use of insect growth regulators such as pyriproxyfen inhibits adult reproduction and blocks the organogenesis of immature larval stages via hormonal or enzymatic actions.²⁰ The combination of an insecticide and an insect growth regulator appears to be most effective in their synergistic actions against adult fleas and larvae. There have been reports of insecticidal resistance in the flea population, especially with pyrethroids.^21,22 A professional exterminator and veterinarian should be consulted. In recalcitrant cases, evaluation for other wild mammals or birds should be performed in unoccupied areas of the home such as the attic, crawl spaces, and basements, as well as inside walls.

Conclusion

The human flea, P irritans, is an important vector in the transmission of human diseases such as the bubonic plague, bartonellosis, and rickettsioses. Flea bites present as intensely pruritic, urticarial to vesicular papules that most commonly present on the lower extremities. Flea bites can be treated with topical steroids, and fleas can be controlled by a combination of insecticidal products and insect growth regulators.

Characteristics

The ubiquitous human flea, Pulex irritans, is a hematophagous wingless ectoparasite in the order Siphonaptera (wingless siphon) that survives by consuming the blood of its mammalian and avian hosts. Due to diseases such as the bubonic plague, fleas have claimed more victims than all the wars ever fought; in the 14th century, the Black Death caused more than 200 million deaths. Fleas fossilized in amber have been found to be 200 million years old and closely resemble the modern human flea, demonstrating the resilience of the species.

The adult human flea is a small, reddish brown, laterally compressed, wingless insect that is approximately 2- to 3.5-mm long (females, 2.5–3.5 mm; males, 2–2.5 mm) and enclosed by a tough cuticle. Compared to the dog flea (Ctenocephalides canis) and cat flea (Ctenocephalides felis), P irritans has no combs or ctenidia (Figure 1). Fleas have large powerful hind legs enabling them to jump horizontally or vertically 200 times their body length (equivalent to a 6-foot human jumping 1200 feet) using stored muscle energy in a pad on the hind legs composed of the elastic protein resilin.¹ They feed off a wide variety of hosts, including humans, pigs, cats, dogs, goats, sheep, cattle, chickens, owls, foxes, rabbits, mice, and feral cats. The flea’s mouthparts are highly specialized for piercing the skin and sucking its blood meal via direct capillary cannulation.

Life Cycle

There are 4 stages of the flea life cycle: egg, larva, pupa, and adult. Most adult flea species mate on the host; the female will lay an average of 4 to 8 small white eggs on the host after each blood meal, laying more than 400 eggs during her lifetime. The eggs then drop from the host and hatch in approximately 4 to 6 days to become larvae. The active larvae feed on available organic matter in their environment, such as their parents’ feces and detritus, while undergoing 3 molts within 1 week to several months.² The larva then spins a silken cocoon from modified salivary glands to form the pupa. In favorable conditions, the pupa lasts only a few weeks; however, it can last for a year or more in unfavorable conditions. Triggers for emergence of the adult flea from the pupa include high humidity, warm temperatures, increased levels of carbon dioxide, and vibrations including sound. An adult P irritans flea can live for a few weeks to more than 1.5 years in favorable conditions of lower air temperature, high relative humidity, and access to a host.³

Related Diseases

Pulex irritans can be a vector for several human diseases. Yersinia pestis is a gram-negative bacteria that causes plague, a highly virulent disease that killed millions of people during its 3 largest human pandemics. The black rat (Rattus rattus) and the oriental rat flea (Xenopsylla cheopis) have been implicated as initial vectors; however, transmission may be human-to-human with pneumonic plague, and septicemic plague may be spread via Pulex fleas or body lice.^4,5 In 1971, Y pestis was isolated from P irritans on a dog in the home of a plague patient in Kayenta, Arizona.⁶Yersinia pestis bacterial DNA also was extracted from P irritans during a plague outbreak in Madagascar in 2014⁷ and was implicated in epidemiologic studies of plague in Tanzania from 1986 to 2004, suggesting it also plays a role in endemic disease.⁸

Bartonellosis is an emerging disease caused by different species of the gram-negative intracellular bacteria of the genus Bartonella transmitted by lice, ticks, and fleas. Bartonella quintana causes trench fever primarily transmitted by the human body louse, Pediculus humanus corporis, and resulted in more than 1 million cases during World War I. Trench fever is characterized by headache, fever, dizziness, and shin pain that lasts 1 to 3 days and recurs in cycles every 4 to 6 days. Other clinical manifestations of B quintana include chronic bacteremia, endocarditis, lymphadenopathy, and bacillary angiomatosis.⁹Bartonella henselae causes cat scratch fever, characterized by lymphadenopathy, fever, headache, joint pain, and lethargy from infected cat scratches or the bite of an infected flea. Bartonella rochalimae also has been found to cause a trench fever–like bacteremia.¹⁰Bartonella species have been found in P irritans, and the flea is implicated as a vector of bartonellosis in humans.^11-15

Rickettsioses are worldwide diseases caused by the gram-negative intracellular bacteria of the genus Rickettsia transmitted to humans via hematophagous arthropods. The rickettsiae traditionally have been classified into the spotted fever or typhus groups. The spotted fever group (ie, Rocky Mountain spotted fever, Mediterranean spotted fever) is transmitted via ticks. The typhus group is transmitted via lice (epidemic typhus) and fleas (endemic or murine typhus). Murine typhus can be caused by Rickettsia typhi in warm coastal areas around the world where the main mammal reservoir is the rat and the rat flea vector X cheopis. Clinical signs of infection are abrupt onset of fever, headaches, myalgia, malaise, and chills, with a truncal maculopapular rash progressing peripherally several days after the initial clinical signs. Rash is present in up to 50% of cases.¹⁶Rickettsia felis is an emerging flea-borne pathogen causing an acute febrile illness usually transmitted via the cat flea C felis.¹⁷Rickettsia species DNA have been found to be present in P irritans from dogs¹⁸ and livestock¹⁹ and pose a risk for causing rickettsioses in humans.

Environmental Treatment and Prevention

Flea bites present as intense, pruritic, urticarial to vesicular papules that usually are located on the lower extremities but also can be present on exposed areas of the upper extremities and hands (Figure 2). Human fleas infest clothing, and bites can be widespread. Topical antipruritics and corticosteroids can be used for controlling itch and the intense cutaneous inflammatory response. The flea host should be identified in areas of the home, school, farm, work, or local environment. House pets should be examined and treated by a veterinarian. The pet’s bedding should be washed and dried at high temperatures, and carpets and floors should be routinely vacuumed or cleaned to remove eggs, larvae, flea feces, and/or pupae. The killing of adult fleas with insecticidal products (eg, imidacloprid, fipronil, spinosad, selamectin, lufenuron, ivermectin) is the primary method of flea control. Use of insect growth regulators such as pyriproxyfen inhibits adult reproduction and blocks the organogenesis of immature larval stages via hormonal or enzymatic actions.²⁰ The combination of an insecticide and an insect growth regulator appears to be most effective in their synergistic actions against adult fleas and larvae. There have been reports of insecticidal resistance in the flea population, especially with pyrethroids.^21,22 A professional exterminator and veterinarian should be consulted. In recalcitrant cases, evaluation for other wild mammals or birds should be performed in unoccupied areas of the home such as the attic, crawl spaces, and basements, as well as inside walls.

Conclusion

The human flea, P irritans, is an important vector in the transmission of human diseases such as the bubonic plague, bartonellosis, and rickettsioses. Flea bites present as intensely pruritic, urticarial to vesicular papules that most commonly present on the lower extremities. Flea bites can be treated with topical steroids, and fleas can be controlled by a combination of insecticidal products and insect growth regulators.

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

Lepidoptera is the second largest order of the class Insecta and comprises approximately 160,000 species of butterflies and moths classified among approximately 124 families and subfamilies. Venomous properties have been identified in 12 of these families, posing a serious threat to human health. ¹

The clinical manifestations from Lepidoptera envenomation can range from general systemic symptoms such as fever and abdominal distress; to more complex focal affections including hemorrhage, ophthalmologic lesions, and irritation of the respiratory tracts; to less severe reactions of the skin, which are the most common presentation.¹

Terminology

Lepidopterism is the term used to address a clinical spectrum of systemic manifestations from direct contact with venomous butterflies or moths and/or their products.² Conversely, erucism is a term used to describe localized cutaneous reactions after direct contact with toxins from caterpillars.

Lepidopterism is derived from the Greek roots lepis, meaning scale, and pteron, meaning wing. The term erucism stems from the Latin word eruca, which means larva.²

Ideally, lepidopterism should refer solely to reactions from butterflies and moths—adult forms of insects with scaly wings—while erucism should refer to reactions from contact with caterpillars—the larval form of butterflies and moths.

In common use, lepidopterism can describe any reaction from caterpillars, moths, or adult butterflies, as well as any case of Lepidoptera exposure with only systemic manifestations, regardless of cutaneous findings. Concurrently, erucism has been defined as either any reaction from caterpillars or any skin reaction from contact with caterpillars or moths.²

Because caterpillars are the larval form of butterflies and moths, caterpillar-associated skin reactions also have been conveniently denominated caterpillar dermatitis.¹ Henceforth in this article, both terms erucism and caterpillar dermatitis are used interchangeably.

Caterpillar Envenomation

Caterpillars cause the vast majority of adverse events from lepidopteran exposures.² Envenomation by caterpillars might stand as the world’s most common envenomation given the larvae proximity to humans.³ Although involvement of internal organs (eg, renal failure), cerebral hemorrhage, and joint lesions can occur, skin manifestations are more predominant with the majority of species. Initial localized pain, edema, and erythema usually are present at the site of direct contact and subsequently progress toward maculopapular to bullous lesions, erosions, petechiae, necrosis, and ulceration depending on the offending species.^1,4

Megalopyge opercularis

In the United States, more than 50 species of caterpillars have been identified as poisonous or venomous.⁵ Megalopyge opercularis (Figure 1), the larval form of the flannel moth, is an important cause of caterpillar-associated dermatitis in the southern United States.^6,7 Megalopyge opercularis also is commonly known as the puss caterpillar, opossum bug, wooly slug, el perrito, tree asp, or Italian asp.⁶ This lepidopteran insect is mainly found in the southeastern and southcentral United States, with noted particular abundance in Texas, Louisiana, and Florida.^6,8 The puss caterpillar has 2 generations per year; the first develops during the months of June to July, and the second develops from September to October, carrying seasonal health hazards.^6,8

Megalopyge opercularis is tapered at the ends and can measure 2.5 to 3.5×1 cm at maturity. It is covered by silky, long-streaked, wavy hairs that may appear single colored or as a mix of colors—from white to gray to brown—forming a mid-dorsal crest.⁶ Beneath this furry coat, rows of short sharp spines are hidden. Upon contact with the human skin, these spines will break and discharge venom.^1,6,8 Toxins contained within the hollow spines are thought to be produced by specialized basal cells, but there still is little knowledge about the dynamics and composition of the venom.¹

Clinical Manifestations

The severity of the reaction depends on the caterpillar’s size and the extent of contact.^1,4 Contact with M opercularis instantly presents with a throbbing or burning pain that may be followed by localized erythema and rash.^1,6 A characteristic gridlike pattern of erythematous macules develops, reflecting each site of puncture from the insect’s spines (Figure 2).^8,9 Skin lesions can progress from erythematous macules to hemorrhagic vesicles or pustules, usually self-resolving after a few days. The reaction also can present with radiating pain to regional lymph nodes and numbness of the affected area.^1,6,8 Moreover, some patients may report urticaria and pruritus.⁹

Envenomation by a puss caterpillar also can present with systemic manifestations including fever, headache, nausea, vomiting, shocklike symptoms, and seizures.^1,6,7 Anaphylactic reaction is rare but also can present.⁷ Uncommon cases have been reported with severe abdominal pain and muscle spasm mimicking acute appendicitis and latrodectism, respectively.^7,9

Diagnosis

The diagnosis of M opercularis envenomation is made clinically based on the morphology of the skin lesions and a history of probable exposure. Coexistent leukocytosis is likely, but laboratory testing is not warranted, as it is both nonspecific and insensitive.⁹

Management/Treatment

The most commonly reported immediate approaches to treatment involve attempts to remove the spines from the skin with tape (stripping), application of ice packs over the affected area, oral antihistamines, topical and intralesional anesthetics, regional nerve block, and oral analgesics.^6,9 There have been several cases detailing the successful use of parenteral calcium gluconate,^5,7 and diazepam has been used to treat severe muscle spasms. Anaphylactic reactions should be managed in a controlled monitored setting with subcutaneous epinephrine.⁷ Despite their common use, some data suggest that ice packs and mid- to high-potency topical steroids are ineffective.⁹

Incidence

From 2001 to 2005, a mean average of 94,552 annual cases of animal bites and stings were reported to poison control centers in the United States, of which 2094 were linked to caterpillars in this 5-year period.¹⁰ There were 3484 M opercularis caterpillar stings reported to the Texas Poison Center Network from 2000 to 2016.^5,6 Given their ability to sting throughout their life cycle, thousands of M opercularis caterpillar stings can occur each year.^1,6 Existing literature on M opercularis caterpillar stings mainly involves case reports with affections of the skin and oral mucosa, self-reported envenomation, and case studies.^5,6,8

Although multiple health concerns associated with caterpillar envenomation have been reported worldwide, the lack of official epidemiologic reports highly suggests that this problem remains underestimated. There also may be many unreported cases because certain reactions are mild or self-limited and can even go unnoticed.¹¹ Nonetheless, there is an evident rise of cases reported in the United States. According to the 2018 annual report of the American Association of Poison Control Centers, there were 2815 case mentions from caterpillar envenomation.¹²

In 1921 and 1952, some public schools in Texas were temporarily closed due to outbreaks of puss caterpillar–associated dermatitis.⁸ Similar outbreaks also have been reported in South Carolina, Virginia, and Oklahoma.⁹ Emerging data suggest that plant oil products and the pesticide cypermethrin may be helpful in controlling local infestations of the puss caterpillar.⁸

Lepidoptera is the second largest order of the class Insecta and comprises approximately 160,000 species of butterflies and moths classified among approximately 124 families and subfamilies. Venomous properties have been identified in 12 of these families, posing a serious threat to human health. ¹

The clinical manifestations from Lepidoptera envenomation can range from general systemic symptoms such as fever and abdominal distress; to more complex focal affections including hemorrhage, ophthalmologic lesions, and irritation of the respiratory tracts; to less severe reactions of the skin, which are the most common presentation.¹

Terminology

Lepidopterism is the term used to address a clinical spectrum of systemic manifestations from direct contact with venomous butterflies or moths and/or their products.² Conversely, erucism is a term used to describe localized cutaneous reactions after direct contact with toxins from caterpillars.

Lepidopterism is derived from the Greek roots lepis, meaning scale, and pteron, meaning wing. The term erucism stems from the Latin word eruca, which means larva.²

Ideally, lepidopterism should refer solely to reactions from butterflies and moths—adult forms of insects with scaly wings—while erucism should refer to reactions from contact with caterpillars—the larval form of butterflies and moths.

In common use, lepidopterism can describe any reaction from caterpillars, moths, or adult butterflies, as well as any case of Lepidoptera exposure with only systemic manifestations, regardless of cutaneous findings. Concurrently, erucism has been defined as either any reaction from caterpillars or any skin reaction from contact with caterpillars or moths.²

Because caterpillars are the larval form of butterflies and moths, caterpillar-associated skin reactions also have been conveniently denominated caterpillar dermatitis.¹ Henceforth in this article, both terms erucism and caterpillar dermatitis are used interchangeably.

Caterpillar Envenomation

Caterpillars cause the vast majority of adverse events from lepidopteran exposures.² Envenomation by caterpillars might stand as the world’s most common envenomation given the larvae proximity to humans.³ Although involvement of internal organs (eg, renal failure), cerebral hemorrhage, and joint lesions can occur, skin manifestations are more predominant with the majority of species. Initial localized pain, edema, and erythema usually are present at the site of direct contact and subsequently progress toward maculopapular to bullous lesions, erosions, petechiae, necrosis, and ulceration depending on the offending species.^1,4

Megalopyge opercularis

In the United States, more than 50 species of caterpillars have been identified as poisonous or venomous.⁵ Megalopyge opercularis (Figure 1), the larval form of the flannel moth, is an important cause of caterpillar-associated dermatitis in the southern United States.^6,7 Megalopyge opercularis also is commonly known as the puss caterpillar, opossum bug, wooly slug, el perrito, tree asp, or Italian asp.⁶ This lepidopteran insect is mainly found in the southeastern and southcentral United States, with noted particular abundance in Texas, Louisiana, and Florida.^6,8 The puss caterpillar has 2 generations per year; the first develops during the months of June to July, and the second develops from September to October, carrying seasonal health hazards.^6,8

Megalopyge opercularis is tapered at the ends and can measure 2.5 to 3.5×1 cm at maturity. It is covered by silky, long-streaked, wavy hairs that may appear single colored or as a mix of colors—from white to gray to brown—forming a mid-dorsal crest.⁶ Beneath this furry coat, rows of short sharp spines are hidden. Upon contact with the human skin, these spines will break and discharge venom.^1,6,8 Toxins contained within the hollow spines are thought to be produced by specialized basal cells, but there still is little knowledge about the dynamics and composition of the venom.¹

Clinical Manifestations

The severity of the reaction depends on the caterpillar’s size and the extent of contact.^1,4 Contact with M opercularis instantly presents with a throbbing or burning pain that may be followed by localized erythema and rash.^1,6 A characteristic gridlike pattern of erythematous macules develops, reflecting each site of puncture from the insect’s spines (Figure 2).^8,9 Skin lesions can progress from erythematous macules to hemorrhagic vesicles or pustules, usually self-resolving after a few days. The reaction also can present with radiating pain to regional lymph nodes and numbness of the affected area.^1,6,8 Moreover, some patients may report urticaria and pruritus.⁹

Envenomation by a puss caterpillar also can present with systemic manifestations including fever, headache, nausea, vomiting, shocklike symptoms, and seizures.^1,6,7 Anaphylactic reaction is rare but also can present.⁷ Uncommon cases have been reported with severe abdominal pain and muscle spasm mimicking acute appendicitis and latrodectism, respectively.^7,9

Diagnosis

The diagnosis of M opercularis envenomation is made clinically based on the morphology of the skin lesions and a history of probable exposure. Coexistent leukocytosis is likely, but laboratory testing is not warranted, as it is both nonspecific and insensitive.⁹

Management/Treatment

The most commonly reported immediate approaches to treatment involve attempts to remove the spines from the skin with tape (stripping), application of ice packs over the affected area, oral antihistamines, topical and intralesional anesthetics, regional nerve block, and oral analgesics.^6,9 There have been several cases detailing the successful use of parenteral calcium gluconate,^5,7 and diazepam has been used to treat severe muscle spasms. Anaphylactic reactions should be managed in a controlled monitored setting with subcutaneous epinephrine.⁷ Despite their common use, some data suggest that ice packs and mid- to high-potency topical steroids are ineffective.⁹

Incidence

From 2001 to 2005, a mean average of 94,552 annual cases of animal bites and stings were reported to poison control centers in the United States, of which 2094 were linked to caterpillars in this 5-year period.¹⁰ There were 3484 M opercularis caterpillar stings reported to the Texas Poison Center Network from 2000 to 2016.^5,6 Given their ability to sting throughout their life cycle, thousands of M opercularis caterpillar stings can occur each year.^1,6 Existing literature on M opercularis caterpillar stings mainly involves case reports with affections of the skin and oral mucosa, self-reported envenomation, and case studies.^5,6,8

Although multiple health concerns associated with caterpillar envenomation have been reported worldwide, the lack of official epidemiologic reports highly suggests that this problem remains underestimated. There also may be many unreported cases because certain reactions are mild or self-limited and can even go unnoticed.¹¹ Nonetheless, there is an evident rise of cases reported in the United States. According to the 2018 annual report of the American Association of Poison Control Centers, there were 2815 case mentions from caterpillar envenomation.¹²

In 1921 and 1952, some public schools in Texas were temporarily closed due to outbreaks of puss caterpillar–associated dermatitis.⁸ Similar outbreaks also have been reported in South Carolina, Virginia, and Oklahoma.⁹ Emerging data suggest that plant oil products and the pesticide cypermethrin may be helpful in controlling local infestations of the puss caterpillar.⁸

Lepidoptera is the second largest order of the class Insecta and comprises approximately 160,000 species of butterflies and moths classified among approximately 124 families and subfamilies. Venomous properties have been identified in 12 of these families, posing a serious threat to human health. ¹

The clinical manifestations from Lepidoptera envenomation can range from general systemic symptoms such as fever and abdominal distress; to more complex focal affections including hemorrhage, ophthalmologic lesions, and irritation of the respiratory tracts; to less severe reactions of the skin, which are the most common presentation.¹

Terminology

Lepidopterism is the term used to address a clinical spectrum of systemic manifestations from direct contact with venomous butterflies or moths and/or their products.² Conversely, erucism is a term used to describe localized cutaneous reactions after direct contact with toxins from caterpillars.

Lepidopterism is derived from the Greek roots lepis, meaning scale, and pteron, meaning wing. The term erucism stems from the Latin word eruca, which means larva.²

Ideally, lepidopterism should refer solely to reactions from butterflies and moths—adult forms of insects with scaly wings—while erucism should refer to reactions from contact with caterpillars—the larval form of butterflies and moths.

In common use, lepidopterism can describe any reaction from caterpillars, moths, or adult butterflies, as well as any case of Lepidoptera exposure with only systemic manifestations, regardless of cutaneous findings. Concurrently, erucism has been defined as either any reaction from caterpillars or any skin reaction from contact with caterpillars or moths.²

Because caterpillars are the larval form of butterflies and moths, caterpillar-associated skin reactions also have been conveniently denominated caterpillar dermatitis.¹ Henceforth in this article, both terms erucism and caterpillar dermatitis are used interchangeably.

Caterpillar Envenomation

Caterpillars cause the vast majority of adverse events from lepidopteran exposures.² Envenomation by caterpillars might stand as the world’s most common envenomation given the larvae proximity to humans.³ Although involvement of internal organs (eg, renal failure), cerebral hemorrhage, and joint lesions can occur, skin manifestations are more predominant with the majority of species. Initial localized pain, edema, and erythema usually are present at the site of direct contact and subsequently progress toward maculopapular to bullous lesions, erosions, petechiae, necrosis, and ulceration depending on the offending species.^1,4

Megalopyge opercularis

In the United States, more than 50 species of caterpillars have been identified as poisonous or venomous.⁵ Megalopyge opercularis (Figure 1), the larval form of the flannel moth, is an important cause of caterpillar-associated dermatitis in the southern United States.^6,7 Megalopyge opercularis also is commonly known as the puss caterpillar, opossum bug, wooly slug, el perrito, tree asp, or Italian asp.⁶ This lepidopteran insect is mainly found in the southeastern and southcentral United States, with noted particular abundance in Texas, Louisiana, and Florida.^6,8 The puss caterpillar has 2 generations per year; the first develops during the months of June to July, and the second develops from September to October, carrying seasonal health hazards.^6,8

Megalopyge opercularis is tapered at the ends and can measure 2.5 to 3.5×1 cm at maturity. It is covered by silky, long-streaked, wavy hairs that may appear single colored or as a mix of colors—from white to gray to brown—forming a mid-dorsal crest.⁶ Beneath this furry coat, rows of short sharp spines are hidden. Upon contact with the human skin, these spines will break and discharge venom.^1,6,8 Toxins contained within the hollow spines are thought to be produced by specialized basal cells, but there still is little knowledge about the dynamics and composition of the venom.¹

Clinical Manifestations

The severity of the reaction depends on the caterpillar’s size and the extent of contact.^1,4 Contact with M opercularis instantly presents with a throbbing or burning pain that may be followed by localized erythema and rash.^1,6 A characteristic gridlike pattern of erythematous macules develops, reflecting each site of puncture from the insect’s spines (Figure 2).^8,9 Skin lesions can progress from erythematous macules to hemorrhagic vesicles or pustules, usually self-resolving after a few days. The reaction also can present with radiating pain to regional lymph nodes and numbness of the affected area.^1,6,8 Moreover, some patients may report urticaria and pruritus.⁹

Envenomation by a puss caterpillar also can present with systemic manifestations including fever, headache, nausea, vomiting, shocklike symptoms, and seizures.^1,6,7 Anaphylactic reaction is rare but also can present.⁷ Uncommon cases have been reported with severe abdominal pain and muscle spasm mimicking acute appendicitis and latrodectism, respectively.^7,9

Diagnosis

The diagnosis of M opercularis envenomation is made clinically based on the morphology of the skin lesions and a history of probable exposure. Coexistent leukocytosis is likely, but laboratory testing is not warranted, as it is both nonspecific and insensitive.⁹

Management/Treatment

The most commonly reported immediate approaches to treatment involve attempts to remove the spines from the skin with tape (stripping), application of ice packs over the affected area, oral antihistamines, topical and intralesional anesthetics, regional nerve block, and oral analgesics.^6,9 There have been several cases detailing the successful use of parenteral calcium gluconate,^5,7 and diazepam has been used to treat severe muscle spasms. Anaphylactic reactions should be managed in a controlled monitored setting with subcutaneous epinephrine.⁷ Despite their common use, some data suggest that ice packs and mid- to high-potency topical steroids are ineffective.⁹

Incidence

From 2001 to 2005, a mean average of 94,552 annual cases of animal bites and stings were reported to poison control centers in the United States, of which 2094 were linked to caterpillars in this 5-year period.¹⁰ There were 3484 M opercularis caterpillar stings reported to the Texas Poison Center Network from 2000 to 2016.^5,6 Given their ability to sting throughout their life cycle, thousands of M opercularis caterpillar stings can occur each year.^1,6 Existing literature on M opercularis caterpillar stings mainly involves case reports with affections of the skin and oral mucosa, self-reported envenomation, and case studies.^5,6,8

Although multiple health concerns associated with caterpillar envenomation have been reported worldwide, the lack of official epidemiologic reports highly suggests that this problem remains underestimated. There also may be many unreported cases because certain reactions are mild or self-limited and can even go unnoticed.¹¹ Nonetheless, there is an evident rise of cases reported in the United States. According to the 2018 annual report of the American Association of Poison Control Centers, there were 2815 case mentions from caterpillar envenomation.¹²

In 1921 and 1952, some public schools in Texas were temporarily closed due to outbreaks of puss caterpillar–associated dermatitis.⁸ Similar outbreaks also have been reported in South Carolina, Virginia, and Oklahoma.⁹ Emerging data suggest that plant oil products and the pesticide cypermethrin may be helpful in controlling local infestations of the puss caterpillar.⁸

Epidemiology and Identification

Centruroides is a common genus of bark scorpions in the United States with at least 21 species considered to be medically important, including the closely related Centruroides exilicauda and Centruroides sculpturatus.¹ Scorpions can be recognized by a bulbous sac and pointed stinger at the end of a tail-like abdomen. They also have long lobsterlike pedipalps (pincers) for grasping their prey. Identifying characteristics for C exilicauda and C sculpturatus include a small, slender, yellow to light brown or tan body typically measuring 1.3 to 7.6 cm in length with a subaculear tooth or tubercle at the base of the stinger, a characteristic that is common to all Centruroides species (Figure).² Some variability in size has been shown, with smaller scorpions found in increased elevations and cooler temperatures.^1,3 Both C exilicauda and C sculpturatus are found in northern Mexico as well as the southwestern United States (eg, Arizona, New Mexico, Texas, California, Nevada).¹ They have a preference for residing in or around trees and often are found on the underside of bark, stones, or tables as well as inside shoes or small cracks and crevices. Scorpions typically sting in self-defense, and stings commonly occur when humans attempt to move tables, put on shoes, or walk barefoot in scorpion-infested areas. Most stings occur from the end of spring through the end summer, but many may go unreported.^1,4

The venom of the Centruroides genus includes peptides and proteins that play a fundamental role in toxic activity by impairing potassium, sodium, and calcium ion channels.^1,3 Toxins have been shown to be species specific, functioning either in capturing prey or deterring predators. Intraspecies variability in toxins has been demonstrated, which may complicate the production of adequate antivenin.³ Many have thought that C exilicauda Wood and C sculpturatus Ewing are the same species, and the names have been used synonymously in the past; however, genetic and biochemical studies of their venom components have shown that they are distinct species and that C sculpturatus is the more dangerous of the two.⁵ The median lethal dose 50% of C sculpturatus was found to be 22.7 μg in CD1 mice.⁶

Envenomation and Clinical Manifestations

Stings from C exilicauda and C sculpturatus have been shown to cause fatality in children more often than in adults.⁷ In the United States, Arizona has the highest frequency of serious symptoms of envenomation as well as the highest hospital and intensive care unit admission rates.⁶ Envenomation results in an immediate sharp burning pain followed by numbness.⁴ Wounds can produce some regional lymph node swelling, ecchymosis, paresthesia, and lymphangitis. More often than not, however, wounds have little to no inflammation and are characterized only by pain.⁴ The puncture wound is too small to be seen, and C exilicauda and C sculpturatus venom do not cause local tissue destruction, an important factor in distinguishing it from other scorpion envenomations.

More severe complications that may follow are caused by the neurotoxin released by Centruroides stings. The toxin components can increase the duration and amplitude of the neuronal action potential and enhance the release of neurotransmitters such as acetylcholine and norepinephrine.⁸ Stings can lead to cranial nerve dysfunction and somatic skeletal neuromuscular dysfunction as well as autonomic dysfunction, specifically salivation, fever, tongue and muscle fasciculations, opsoclonus, vomiting, bronchoconstriction, diaphoresis, nystagmus, blurred vision, slurred speech, hypertension, rhabdomyolysis, stridor, wheezing, aspiration, anaphylaxis, and tachycardia, leading to cardiac and respiratory compromise.^4,8 Some patients have experienced a decreased sense of smell or hearing and decreased fine motor movements.⁷ Although pancreatitis may occur with scorpion stings, it is not common for C exilicauda.⁹ Comorbidities such as cardiac disease and substance use disorders contribute to prolonged length of hospital stay and poor outcome.⁸

Treatment

Most Centruroides stings can be managed at home, but patients with more serious symptoms and children younger than 2 years should be taken to a hospital for treatment.⁷ If a patient reports only pain but shows no other signs of neurotoxicity, observation and pain relief with rest, ice, and elevation is appropriate management. Patients with severe manifestations have been treated with various combinations of lorazepam, glycopyrrolate, ipratropium bromide, and ondansetron, but the only treatment definitively shown to decrease time to symptom abatement is antivenin.⁷ It has been demonstrated that C exilicauda and C sculpturatus antivenin is relatively safe.⁷ Most patients, especially adults, do not die from C exilicauda and C sculpturatus stings; therefore, antivenin more commonly is symptom abating than it is lifesaving.¹⁰ In children, time to symptom resolution was decreased to fewer than 4 hours with antivenin, and there is a lower rate of inpatient admission when antivenin is administered.^4,10,11 There is a low incidence of anaphylactic reaction after antivenin, but there have been reported cases of self-limited serum sickness after antivenin use that generally can be managed with antihistamines and corticosteroids.^4,7

Epidemiology and Identification

Centruroides is a common genus of bark scorpions in the United States with at least 21 species considered to be medically important, including the closely related Centruroides exilicauda and Centruroides sculpturatus.¹ Scorpions can be recognized by a bulbous sac and pointed stinger at the end of a tail-like abdomen. They also have long lobsterlike pedipalps (pincers) for grasping their prey. Identifying characteristics for C exilicauda and C sculpturatus include a small, slender, yellow to light brown or tan body typically measuring 1.3 to 7.6 cm in length with a subaculear tooth or tubercle at the base of the stinger, a characteristic that is common to all Centruroides species (Figure).² Some variability in size has been shown, with smaller scorpions found in increased elevations and cooler temperatures.^1,3 Both C exilicauda and C sculpturatus are found in northern Mexico as well as the southwestern United States (eg, Arizona, New Mexico, Texas, California, Nevada).¹ They have a preference for residing in or around trees and often are found on the underside of bark, stones, or tables as well as inside shoes or small cracks and crevices. Scorpions typically sting in self-defense, and stings commonly occur when humans attempt to move tables, put on shoes, or walk barefoot in scorpion-infested areas. Most stings occur from the end of spring through the end summer, but many may go unreported.^1,4

The venom of the Centruroides genus includes peptides and proteins that play a fundamental role in toxic activity by impairing potassium, sodium, and calcium ion channels.^1,3 Toxins have been shown to be species specific, functioning either in capturing prey or deterring predators. Intraspecies variability in toxins has been demonstrated, which may complicate the production of adequate antivenin.³ Many have thought that C exilicauda Wood and C sculpturatus Ewing are the same species, and the names have been used synonymously in the past; however, genetic and biochemical studies of their venom components have shown that they are distinct species and that C sculpturatus is the more dangerous of the two.⁵ The median lethal dose 50% of C sculpturatus was found to be 22.7 μg in CD1 mice.⁶

Envenomation and Clinical Manifestations

Stings from C exilicauda and C sculpturatus have been shown to cause fatality in children more often than in adults.⁷ In the United States, Arizona has the highest frequency of serious symptoms of envenomation as well as the highest hospital and intensive care unit admission rates.⁶ Envenomation results in an immediate sharp burning pain followed by numbness.⁴ Wounds can produce some regional lymph node swelling, ecchymosis, paresthesia, and lymphangitis. More often than not, however, wounds have little to no inflammation and are characterized only by pain.⁴ The puncture wound is too small to be seen, and C exilicauda and C sculpturatus venom do not cause local tissue destruction, an important factor in distinguishing it from other scorpion envenomations.

More severe complications that may follow are caused by the neurotoxin released by Centruroides stings. The toxin components can increase the duration and amplitude of the neuronal action potential and enhance the release of neurotransmitters such as acetylcholine and norepinephrine.⁸ Stings can lead to cranial nerve dysfunction and somatic skeletal neuromuscular dysfunction as well as autonomic dysfunction, specifically salivation, fever, tongue and muscle fasciculations, opsoclonus, vomiting, bronchoconstriction, diaphoresis, nystagmus, blurred vision, slurred speech, hypertension, rhabdomyolysis, stridor, wheezing, aspiration, anaphylaxis, and tachycardia, leading to cardiac and respiratory compromise.^4,8 Some patients have experienced a decreased sense of smell or hearing and decreased fine motor movements.⁷ Although pancreatitis may occur with scorpion stings, it is not common for C exilicauda.⁹ Comorbidities such as cardiac disease and substance use disorders contribute to prolonged length of hospital stay and poor outcome.⁸

Treatment

Most Centruroides stings can be managed at home, but patients with more serious symptoms and children younger than 2 years should be taken to a hospital for treatment.⁷ If a patient reports only pain but shows no other signs of neurotoxicity, observation and pain relief with rest, ice, and elevation is appropriate management. Patients with severe manifestations have been treated with various combinations of lorazepam, glycopyrrolate, ipratropium bromide, and ondansetron, but the only treatment definitively shown to decrease time to symptom abatement is antivenin.⁷ It has been demonstrated that C exilicauda and C sculpturatus antivenin is relatively safe.⁷ Most patients, especially adults, do not die from C exilicauda and C sculpturatus stings; therefore, antivenin more commonly is symptom abating than it is lifesaving.¹⁰ In children, time to symptom resolution was decreased to fewer than 4 hours with antivenin, and there is a lower rate of inpatient admission when antivenin is administered.^4,10,11 There is a low incidence of anaphylactic reaction after antivenin, but there have been reported cases of self-limited serum sickness after antivenin use that generally can be managed with antihistamines and corticosteroids.^4,7

Epidemiology and Identification

Centruroides is a common genus of bark scorpions in the United States with at least 21 species considered to be medically important, including the closely related Centruroides exilicauda and Centruroides sculpturatus.¹ Scorpions can be recognized by a bulbous sac and pointed stinger at the end of a tail-like abdomen. They also have long lobsterlike pedipalps (pincers) for grasping their prey. Identifying characteristics for C exilicauda and C sculpturatus include a small, slender, yellow to light brown or tan body typically measuring 1.3 to 7.6 cm in length with a subaculear tooth or tubercle at the base of the stinger, a characteristic that is common to all Centruroides species (Figure).² Some variability in size has been shown, with smaller scorpions found in increased elevations and cooler temperatures.^1,3 Both C exilicauda and C sculpturatus are found in northern Mexico as well as the southwestern United States (eg, Arizona, New Mexico, Texas, California, Nevada).¹ They have a preference for residing in or around trees and often are found on the underside of bark, stones, or tables as well as inside shoes or small cracks and crevices. Scorpions typically sting in self-defense, and stings commonly occur when humans attempt to move tables, put on shoes, or walk barefoot in scorpion-infested areas. Most stings occur from the end of spring through the end summer, but many may go unreported.^1,4

The venom of the Centruroides genus includes peptides and proteins that play a fundamental role in toxic activity by impairing potassium, sodium, and calcium ion channels.^1,3 Toxins have been shown to be species specific, functioning either in capturing prey or deterring predators. Intraspecies variability in toxins has been demonstrated, which may complicate the production of adequate antivenin.³ Many have thought that C exilicauda Wood and C sculpturatus Ewing are the same species, and the names have been used synonymously in the past; however, genetic and biochemical studies of their venom components have shown that they are distinct species and that C sculpturatus is the more dangerous of the two.⁵ The median lethal dose 50% of C sculpturatus was found to be 22.7 μg in CD1 mice.⁶

Envenomation and Clinical Manifestations

Stings from C exilicauda and C sculpturatus have been shown to cause fatality in children more often than in adults.⁷ In the United States, Arizona has the highest frequency of serious symptoms of envenomation as well as the highest hospital and intensive care unit admission rates.⁶ Envenomation results in an immediate sharp burning pain followed by numbness.⁴ Wounds can produce some regional lymph node swelling, ecchymosis, paresthesia, and lymphangitis. More often than not, however, wounds have little to no inflammation and are characterized only by pain.⁴ The puncture wound is too small to be seen, and C exilicauda and C sculpturatus venom do not cause local tissue destruction, an important factor in distinguishing it from other scorpion envenomations.

More severe complications that may follow are caused by the neurotoxin released by Centruroides stings. The toxin components can increase the duration and amplitude of the neuronal action potential and enhance the release of neurotransmitters such as acetylcholine and norepinephrine.⁸ Stings can lead to cranial nerve dysfunction and somatic skeletal neuromuscular dysfunction as well as autonomic dysfunction, specifically salivation, fever, tongue and muscle fasciculations, opsoclonus, vomiting, bronchoconstriction, diaphoresis, nystagmus, blurred vision, slurred speech, hypertension, rhabdomyolysis, stridor, wheezing, aspiration, anaphylaxis, and tachycardia, leading to cardiac and respiratory compromise.^4,8 Some patients have experienced a decreased sense of smell or hearing and decreased fine motor movements.⁷ Although pancreatitis may occur with scorpion stings, it is not common for C exilicauda.⁹ Comorbidities such as cardiac disease and substance use disorders contribute to prolonged length of hospital stay and poor outcome.⁸

Treatment

Most Centruroides stings can be managed at home, but patients with more serious symptoms and children younger than 2 years should be taken to a hospital for treatment.⁷ If a patient reports only pain but shows no other signs of neurotoxicity, observation and pain relief with rest, ice, and elevation is appropriate management. Patients with severe manifestations have been treated with various combinations of lorazepam, glycopyrrolate, ipratropium bromide, and ondansetron, but the only treatment definitively shown to decrease time to symptom abatement is antivenin.⁷ It has been demonstrated that C exilicauda and C sculpturatus antivenin is relatively safe.⁷ Most patients, especially adults, do not die from C exilicauda and C sculpturatus stings; therefore, antivenin more commonly is symptom abating than it is lifesaving.¹⁰ In children, time to symptom resolution was decreased to fewer than 4 hours with antivenin, and there is a lower rate of inpatient admission when antivenin is administered.^4,10,11 There is a low incidence of anaphylactic reaction after antivenin, but there have been reported cases of self-limited serum sickness after antivenin use that generally can be managed with antihistamines and corticosteroids.^4,7

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²