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Author(s)
Bonnie D. Hodge, MD
George W. Elgart, MD
Dirk M. Elston, MD

 

Classification

Blister beetles are both a scourge and the source of medical cantharidin (Figure 1). The term blister beetle refers to 3 families of the order Coleoptera: Meloidae, Oedemeridae, and Staphylinidae (Figure 2).

Figure 1. Blister beetles

Figure 2. A simplified taxonomy of blister beetles

Meloidae is the most well-known family of blister beetles, with more than 200 species worldwide identified as a cause of blistering dermatitis.1 The most notorious is Lytta vesicatoria, also known as the Spanish fly. Although some blister beetles are inconspicuous in appearance, most are brightly colored and easily spotted, making them attractive to small children.2 They may be attracted to fluorescent lighting and commonly enter through open windows.3 Blister beetles do not bite or sting; rather, they release cantharidin via hemolymph, an oily yellow substance that is copiously expressed from the leg joints when disturbed by rubbing or pressing.1,3-5 Blistering also is associated with exposure to the contents of crushed beetles, which is the source of pharmacologic cantharidin.2,4,6



Oedemeridae are the smallest and least known beetles within the Coleoptera family. They often are called false blister beetles, which is a misnomer. Oedemeridae beetles also produce cantharidin, similar to Meloidae beetles; however, because Oedemeridae beetles are smaller, the vesiculobullous eruptions also are less pronounced.1

A third well-known family of blister beetles is the Staphylinidae family. Rove beetles (genus Paederus) differ from the Meloidae and Oedemeridae families in that they produce the vesicant pederin rather than cantharidin. Pederin causes a more violent eruption called dermatitis linearis, which often is associated with intense urticaria prior to blistering.1 Rove beetles are found in moist environments and tend to favor tropical and subtropical climates. They may emerge in large numbers after heavy rainfall.

Clinical Presentation

Blistering dermatitis—caused by exposure to cantharidin (families Meloidae and Oedemeridae) or pederin (genus Paederus)—begins as burning and tingling within minutes of exposure. Bullae later develop, often in a linear fashion, with subsequent bursting and crust formation.1,3 Secondary infection can occur.5 Exposure occurring on the elbows, knees, or mirroring skin folds results in lesions on opposing surfaces that come into contact, otherwise known as kissing lesions.1,3 Acantholysis of suprabasal keratinocytes can be seen on histologic sections of blisters (Figure 3)1,7 due to cantharidin activation of the serine/threonine protein phosphatases that cause detachment of tonofilaments from desmosomes.1,8 Washing of exposed sites with soap or alcohol can potentially prevent development of blistering dermatitis; however, lesions usually heal without complication when treated with topical antibiotics.3

Figure 3. Typical histopathologic features of a dermatologic reaction to cantharidin (H&E, original magnification ×200). An intraepidermal vesicle demonstrating both acantholysis (as in pemphigus vulgaris) and superficial necrosis (as in a toxic response to topical agents). These features are typical for a reaction to cantharone, the active ingredient in blister beetle fluid.

 

 

If blister beetles are ingested, they can cause poisoning characterized by abdominal pain and hematuria.1,3,9,10 In fact, blister beetle ingestion by animals consuming baled hay is an important agricultural and economical implication. Several cases of fatal farm animal ingestion resulting in gastrointestinal erosion have been reported.4,6

Medicinal Properties

Medicinal use of cantharidin has been recorded as early as the 19th century and is believed to have been part of ancient medicinal practices in China, Spain, South Africa, and pre-Columbian America for its vesicant, abortifacient, and supposed aphrodisiac properties.2,4,8

Toxicity from internal ingestion has been well documented.1,3,9,10 The Mylabris and Epicauta genera of the family Meloidae, most commonly the Spanish fly, are used for modern extraction of cantharidin. Up to 5% of the dry weight of a blister beetle can be constituted by cantharidin.4

Although its use has diminished due to limited availability, cantharidin is still used for treatment of common warts, periungual warts, and molluscum contagiosum. It is a favorable choice for treating pediatric patients because of the tolerability and painlessness of application. Due to its acantholytic properties, warts generally slough with the cantharidin-induced blister.11



In recent years, cantharidin has been studied for its anticancer properties. It has been shown to weaken cancer cell antioxidant properties by interfering with glutathione-related enzymes, thus inducing oxidative damage. Additionally, cantharidin is associated with decreased mitochondrial cytochrome C and increased cytosolic cytochrome C, an important signal for apoptosis.12 Furthermore, cantharidin recently was shown to increase expression of proapoptotic proteins and decrease expression of antiapoptotic proteins causing cell death in nasopharyngeal carcinoma, making it a potential anticancer treatment.13

Conclusion

Blister beetles, long known for their production of vesicant agents, are both a cause of as well as a potential treatment of dermatologic disease. The blistering associated with exposure to a disturbed beetle generally is mild and heals without scarring if vital areas such as the eyelids are not affected.

References
  1. Nicholls DS, Christmas TI, Greig DE. Oedemerid blister beetle dermatosis: a review. J Am Acad Dermatol. 1990;22:815-819.
  2. Percino-Daniel N, Buckley D, García-París M. Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity, traditions, and mitochondrial DNA. J Ethnopharmacol. 2013;147:570-583.
  3. James WD, Berger TG, Elston DM. Parasitic infestations, stings, and bites. In: James WD, Berger TG, Elston DM, eds. Andrew’s Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:418-450.
  4. Selander RB, Fasulo TR. Featured creatures: blister beetles. University of Florida/IFAS Entomology and Nematology website. http://entnemdept.ufl.edu/creatures/urban/medical/blister_beetles.htm. Published October 2000. Revised September 2010. Accessed November 12, 2019.
  5. Wijerathne BTB. Blister mystery. Wilderness Environ Med. 2017;28:271-272.
  6. Penrith ML, Naude TW. Mortality in chickens associated with blister beetle consumption. J S Afr Vet Assoc. 1996;67:97-99.
  7. Yell JA, Burge SM, Dean D. Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins. Br J Dermatol. 1994;130:148-157.
  8. Honkanen RE. Cantharidin, another natural toxin that inhibits the activity of serine-threonine protein phosphatases types 1 and 2a. FEBS Letters. 1993;330:283-286.
  9. Al-Binali AM, Shabana M, Al-Fifi S, et al. Cantharidin poisoning due to blister beetle ingestion in children: two case reports and a review of clinical presentations. Sultan Qaboos Univ Med J. 2010;10:258-261.
  10. Tagwireyi D, Ball DE, Loga PJ, et al. Cantharidin poisoning due to “blister beetle” ingestion. Toxicon. 2000;38:1865-1869.
  11. Al-Dawsari NA, Masterpol KS. Cantharidin in dermatology. Skinmed. 2016;14:111-114.
  12. Verma AK, Prasad SB. Changes in glutathione, oxidative stress and mitochondrial membrane potential in apoptosis involving the anticancer activity of cantharidin isolated from redheaded blister beetles, epicauta hirticornis. Anticancer Agents Med Chem. 2013;13:1096-1114.
  13. Chen AW, Tseng YS, Lin CC, et al. Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway. Environ Toxicol. 2018;33:343-350.
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Dr. Hodge is from the School of Medicine, University of Mississippi Medical Center, Jackson. Dr. Elgart is from the Department of Dermatology, University of Miami, Florida. Dr. Elston is from the Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston.

The authors report no conflict of interest.

Figure 1 is in the public domain.

Correspondence: Bonnie D. Hodge, MD, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216 (bhodge2@umc.edu).

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Author(s)
Bonnie D. Hodge, MD
George W. Elgart, MD
Dirk M. Elston, MD
Author(s)
Bonnie D. Hodge, MD
George W. Elgart, MD
Dirk M. Elston, MD
Author and Disclosure Information

Dr. Hodge is from the School of Medicine, University of Mississippi Medical Center, Jackson. Dr. Elgart is from the Department of Dermatology, University of Miami, Florida. Dr. Elston is from the Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston.

The authors report no conflict of interest.

Figure 1 is in the public domain.

Correspondence: Bonnie D. Hodge, MD, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216 (bhodge2@umc.edu).

Author and Disclosure Information

Dr. Hodge is from the School of Medicine, University of Mississippi Medical Center, Jackson. Dr. Elgart is from the Department of Dermatology, University of Miami, Florida. Dr. Elston is from the Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston.

The authors report no conflict of interest.

Figure 1 is in the public domain.

Correspondence: Bonnie D. Hodge, MD, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216 (bhodge2@umc.edu).

Article PDF
Hodge beetle CT104006317.PDF
Article PDF
Hodge beetle CT104006317.PDF

 

Classification

Blister beetles are both a scourge and the source of medical cantharidin (Figure 1). The term blister beetle refers to 3 families of the order Coleoptera: Meloidae, Oedemeridae, and Staphylinidae (Figure 2).

Figure 1. Blister beetles

Figure 2. A simplified taxonomy of blister beetles

Meloidae is the most well-known family of blister beetles, with more than 200 species worldwide identified as a cause of blistering dermatitis.1 The most notorious is Lytta vesicatoria, also known as the Spanish fly. Although some blister beetles are inconspicuous in appearance, most are brightly colored and easily spotted, making them attractive to small children.2 They may be attracted to fluorescent lighting and commonly enter through open windows.3 Blister beetles do not bite or sting; rather, they release cantharidin via hemolymph, an oily yellow substance that is copiously expressed from the leg joints when disturbed by rubbing or pressing.1,3-5 Blistering also is associated with exposure to the contents of crushed beetles, which is the source of pharmacologic cantharidin.2,4,6



Oedemeridae are the smallest and least known beetles within the Coleoptera family. They often are called false blister beetles, which is a misnomer. Oedemeridae beetles also produce cantharidin, similar to Meloidae beetles; however, because Oedemeridae beetles are smaller, the vesiculobullous eruptions also are less pronounced.1

A third well-known family of blister beetles is the Staphylinidae family. Rove beetles (genus Paederus) differ from the Meloidae and Oedemeridae families in that they produce the vesicant pederin rather than cantharidin. Pederin causes a more violent eruption called dermatitis linearis, which often is associated with intense urticaria prior to blistering.1 Rove beetles are found in moist environments and tend to favor tropical and subtropical climates. They may emerge in large numbers after heavy rainfall.

Clinical Presentation

Blistering dermatitis—caused by exposure to cantharidin (families Meloidae and Oedemeridae) or pederin (genus Paederus)—begins as burning and tingling within minutes of exposure. Bullae later develop, often in a linear fashion, with subsequent bursting and crust formation.1,3 Secondary infection can occur.5 Exposure occurring on the elbows, knees, or mirroring skin folds results in lesions on opposing surfaces that come into contact, otherwise known as kissing lesions.1,3 Acantholysis of suprabasal keratinocytes can be seen on histologic sections of blisters (Figure 3)1,7 due to cantharidin activation of the serine/threonine protein phosphatases that cause detachment of tonofilaments from desmosomes.1,8 Washing of exposed sites with soap or alcohol can potentially prevent development of blistering dermatitis; however, lesions usually heal without complication when treated with topical antibiotics.3

Figure 3. Typical histopathologic features of a dermatologic reaction to cantharidin (H&E, original magnification ×200). An intraepidermal vesicle demonstrating both acantholysis (as in pemphigus vulgaris) and superficial necrosis (as in a toxic response to topical agents). These features are typical for a reaction to cantharone, the active ingredient in blister beetle fluid.

 

 

If blister beetles are ingested, they can cause poisoning characterized by abdominal pain and hematuria.1,3,9,10 In fact, blister beetle ingestion by animals consuming baled hay is an important agricultural and economical implication. Several cases of fatal farm animal ingestion resulting in gastrointestinal erosion have been reported.4,6

Medicinal Properties

Medicinal use of cantharidin has been recorded as early as the 19th century and is believed to have been part of ancient medicinal practices in China, Spain, South Africa, and pre-Columbian America for its vesicant, abortifacient, and supposed aphrodisiac properties.2,4,8

Toxicity from internal ingestion has been well documented.1,3,9,10 The Mylabris and Epicauta genera of the family Meloidae, most commonly the Spanish fly, are used for modern extraction of cantharidin. Up to 5% of the dry weight of a blister beetle can be constituted by cantharidin.4

Although its use has diminished due to limited availability, cantharidin is still used for treatment of common warts, periungual warts, and molluscum contagiosum. It is a favorable choice for treating pediatric patients because of the tolerability and painlessness of application. Due to its acantholytic properties, warts generally slough with the cantharidin-induced blister.11



In recent years, cantharidin has been studied for its anticancer properties. It has been shown to weaken cancer cell antioxidant properties by interfering with glutathione-related enzymes, thus inducing oxidative damage. Additionally, cantharidin is associated with decreased mitochondrial cytochrome C and increased cytosolic cytochrome C, an important signal for apoptosis.12 Furthermore, cantharidin recently was shown to increase expression of proapoptotic proteins and decrease expression of antiapoptotic proteins causing cell death in nasopharyngeal carcinoma, making it a potential anticancer treatment.13

Conclusion

Blister beetles, long known for their production of vesicant agents, are both a cause of as well as a potential treatment of dermatologic disease. The blistering associated with exposure to a disturbed beetle generally is mild and heals without scarring if vital areas such as the eyelids are not affected.

 

Classification

Blister beetles are both a scourge and the source of medical cantharidin (Figure 1). The term blister beetle refers to 3 families of the order Coleoptera: Meloidae, Oedemeridae, and Staphylinidae (Figure 2).

Figure 1. Blister beetles

Figure 2. A simplified taxonomy of blister beetles

Meloidae is the most well-known family of blister beetles, with more than 200 species worldwide identified as a cause of blistering dermatitis.1 The most notorious is Lytta vesicatoria, also known as the Spanish fly. Although some blister beetles are inconspicuous in appearance, most are brightly colored and easily spotted, making them attractive to small children.2 They may be attracted to fluorescent lighting and commonly enter through open windows.3 Blister beetles do not bite or sting; rather, they release cantharidin via hemolymph, an oily yellow substance that is copiously expressed from the leg joints when disturbed by rubbing or pressing.1,3-5 Blistering also is associated with exposure to the contents of crushed beetles, which is the source of pharmacologic cantharidin.2,4,6



Oedemeridae are the smallest and least known beetles within the Coleoptera family. They often are called false blister beetles, which is a misnomer. Oedemeridae beetles also produce cantharidin, similar to Meloidae beetles; however, because Oedemeridae beetles are smaller, the vesiculobullous eruptions also are less pronounced.1

A third well-known family of blister beetles is the Staphylinidae family. Rove beetles (genus Paederus) differ from the Meloidae and Oedemeridae families in that they produce the vesicant pederin rather than cantharidin. Pederin causes a more violent eruption called dermatitis linearis, which often is associated with intense urticaria prior to blistering.1 Rove beetles are found in moist environments and tend to favor tropical and subtropical climates. They may emerge in large numbers after heavy rainfall.

Clinical Presentation

Blistering dermatitis—caused by exposure to cantharidin (families Meloidae and Oedemeridae) or pederin (genus Paederus)—begins as burning and tingling within minutes of exposure. Bullae later develop, often in a linear fashion, with subsequent bursting and crust formation.1,3 Secondary infection can occur.5 Exposure occurring on the elbows, knees, or mirroring skin folds results in lesions on opposing surfaces that come into contact, otherwise known as kissing lesions.1,3 Acantholysis of suprabasal keratinocytes can be seen on histologic sections of blisters (Figure 3)1,7 due to cantharidin activation of the serine/threonine protein phosphatases that cause detachment of tonofilaments from desmosomes.1,8 Washing of exposed sites with soap or alcohol can potentially prevent development of blistering dermatitis; however, lesions usually heal without complication when treated with topical antibiotics.3

Figure 3. Typical histopathologic features of a dermatologic reaction to cantharidin (H&E, original magnification ×200). An intraepidermal vesicle demonstrating both acantholysis (as in pemphigus vulgaris) and superficial necrosis (as in a toxic response to topical agents). These features are typical for a reaction to cantharone, the active ingredient in blister beetle fluid.

 

 

If blister beetles are ingested, they can cause poisoning characterized by abdominal pain and hematuria.1,3,9,10 In fact, blister beetle ingestion by animals consuming baled hay is an important agricultural and economical implication. Several cases of fatal farm animal ingestion resulting in gastrointestinal erosion have been reported.4,6

Medicinal Properties

Medicinal use of cantharidin has been recorded as early as the 19th century and is believed to have been part of ancient medicinal practices in China, Spain, South Africa, and pre-Columbian America for its vesicant, abortifacient, and supposed aphrodisiac properties.2,4,8

Toxicity from internal ingestion has been well documented.1,3,9,10 The Mylabris and Epicauta genera of the family Meloidae, most commonly the Spanish fly, are used for modern extraction of cantharidin. Up to 5% of the dry weight of a blister beetle can be constituted by cantharidin.4

Although its use has diminished due to limited availability, cantharidin is still used for treatment of common warts, periungual warts, and molluscum contagiosum. It is a favorable choice for treating pediatric patients because of the tolerability and painlessness of application. Due to its acantholytic properties, warts generally slough with the cantharidin-induced blister.11



In recent years, cantharidin has been studied for its anticancer properties. It has been shown to weaken cancer cell antioxidant properties by interfering with glutathione-related enzymes, thus inducing oxidative damage. Additionally, cantharidin is associated with decreased mitochondrial cytochrome C and increased cytosolic cytochrome C, an important signal for apoptosis.12 Furthermore, cantharidin recently was shown to increase expression of proapoptotic proteins and decrease expression of antiapoptotic proteins causing cell death in nasopharyngeal carcinoma, making it a potential anticancer treatment.13

Conclusion

Blister beetles, long known for their production of vesicant agents, are both a cause of as well as a potential treatment of dermatologic disease. The blistering associated with exposure to a disturbed beetle generally is mild and heals without scarring if vital areas such as the eyelids are not affected.

References
  1. Nicholls DS, Christmas TI, Greig DE. Oedemerid blister beetle dermatosis: a review. J Am Acad Dermatol. 1990;22:815-819.
  2. Percino-Daniel N, Buckley D, García-París M. Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity, traditions, and mitochondrial DNA. J Ethnopharmacol. 2013;147:570-583.
  3. James WD, Berger TG, Elston DM. Parasitic infestations, stings, and bites. In: James WD, Berger TG, Elston DM, eds. Andrew’s Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:418-450.
  4. Selander RB, Fasulo TR. Featured creatures: blister beetles. University of Florida/IFAS Entomology and Nematology website. http://entnemdept.ufl.edu/creatures/urban/medical/blister_beetles.htm. Published October 2000. Revised September 2010. Accessed November 12, 2019.
  5. Wijerathne BTB. Blister mystery. Wilderness Environ Med. 2017;28:271-272.
  6. Penrith ML, Naude TW. Mortality in chickens associated with blister beetle consumption. J S Afr Vet Assoc. 1996;67:97-99.
  7. Yell JA, Burge SM, Dean D. Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins. Br J Dermatol. 1994;130:148-157.
  8. Honkanen RE. Cantharidin, another natural toxin that inhibits the activity of serine-threonine protein phosphatases types 1 and 2a. FEBS Letters. 1993;330:283-286.
  9. Al-Binali AM, Shabana M, Al-Fifi S, et al. Cantharidin poisoning due to blister beetle ingestion in children: two case reports and a review of clinical presentations. Sultan Qaboos Univ Med J. 2010;10:258-261.
  10. Tagwireyi D, Ball DE, Loga PJ, et al. Cantharidin poisoning due to “blister beetle” ingestion. Toxicon. 2000;38:1865-1869.
  11. Al-Dawsari NA, Masterpol KS. Cantharidin in dermatology. Skinmed. 2016;14:111-114.
  12. Verma AK, Prasad SB. Changes in glutathione, oxidative stress and mitochondrial membrane potential in apoptosis involving the anticancer activity of cantharidin isolated from redheaded blister beetles, epicauta hirticornis. Anticancer Agents Med Chem. 2013;13:1096-1114.
  13. Chen AW, Tseng YS, Lin CC, et al. Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway. Environ Toxicol. 2018;33:343-350.
References
  1. Nicholls DS, Christmas TI, Greig DE. Oedemerid blister beetle dermatosis: a review. J Am Acad Dermatol. 1990;22:815-819.
  2. Percino-Daniel N, Buckley D, García-París M. Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity, traditions, and mitochondrial DNA. J Ethnopharmacol. 2013;147:570-583.
  3. James WD, Berger TG, Elston DM. Parasitic infestations, stings, and bites. In: James WD, Berger TG, Elston DM, eds. Andrew’s Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:418-450.
  4. Selander RB, Fasulo TR. Featured creatures: blister beetles. University of Florida/IFAS Entomology and Nematology website. http://entnemdept.ufl.edu/creatures/urban/medical/blister_beetles.htm. Published October 2000. Revised September 2010. Accessed November 12, 2019.
  5. Wijerathne BTB. Blister mystery. Wilderness Environ Med. 2017;28:271-272.
  6. Penrith ML, Naude TW. Mortality in chickens associated with blister beetle consumption. J S Afr Vet Assoc. 1996;67:97-99.
  7. Yell JA, Burge SM, Dean D. Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins. Br J Dermatol. 1994;130:148-157.
  8. Honkanen RE. Cantharidin, another natural toxin that inhibits the activity of serine-threonine protein phosphatases types 1 and 2a. FEBS Letters. 1993;330:283-286.
  9. Al-Binali AM, Shabana M, Al-Fifi S, et al. Cantharidin poisoning due to blister beetle ingestion in children: two case reports and a review of clinical presentations. Sultan Qaboos Univ Med J. 2010;10:258-261.
  10. Tagwireyi D, Ball DE, Loga PJ, et al. Cantharidin poisoning due to “blister beetle” ingestion. Toxicon. 2000;38:1865-1869.
  11. Al-Dawsari NA, Masterpol KS. Cantharidin in dermatology. Skinmed. 2016;14:111-114.
  12. Verma AK, Prasad SB. Changes in glutathione, oxidative stress and mitochondrial membrane potential in apoptosis involving the anticancer activity of cantharidin isolated from redheaded blister beetles, epicauta hirticornis. Anticancer Agents Med Chem. 2013;13:1096-1114.
  13. Chen AW, Tseng YS, Lin CC, et al. Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway. Environ Toxicol. 2018;33:343-350.
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Practice Points

  • Exposure to cantharidin presents initially with burning and tingling before progressing to bullae formation, sometimes in a linear fashion. Rupture of bullae and crust formation can occur.
  • Washing of the exposed skin with soap and water may prevent development of blistering dermatitis.
  • Clinical use of cantharidin is favorable in treating pediatric patients with common warts and molluscum contagiosum due to tolerability and painlessness of application.
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