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Immediate, late, and delayed skin test responses to Centruroides vittatus scorpion venom

1995; Elsevier BV; Volume: 95; Issue: 1 Linguagem: Inglês

10.1016/s0091-6749(95)70163-x

1097-6825

Jeffrey G. Demain, David W. Goetz,

Insect and Pesticide Research

As one of 40 species inhabiting the United States, the common Texas striped scorpion, Centruroides vittatus, produces a low toxicity venom,1Keegan HL Lockwood WR Secretory epithelium in venom glands of two species of scorpions of the genus Centruroides marx.Am J Trop Med Hyg. 1971; 20: 770-785PubMed Google Scholar which usually causes immediate sharp pain and local swelling after a sting. Venom neurotoxins may also produce skeletal muscle spasms and paresthesias, particularly of the sting site, face, and tongue.2Rochat H Scorpion toxin and mode of action.Adv Cytopharmacol. 1979; 3: 325-334PubMed Google Scholar Immunologic reactions to envenomation have not been well documented.CASE REPORTSSeven patients with a history of C. vittatus envenomation and six control subjects were evaluated by prick and intradermal skin testing with C. vittatus venom. Three subjects had a history of immediate anaphylactic reactions to envenomation.Case 1The patient was a 38-year-old woman with a history of five episodes of scorpion envenomation. Each of the three most recent episodes, which occurred within a single 30-day period, resulted in immediate local pain, which was followed in minutes by regional paresthesias, chest tightness, wheezing, nausea, vomiting, dizziness, and light-headedness.Case 2The patient was a 53-year-old woman with a history of two episodes of scorpion envenomation. The first sting resulted in a large local reaction (LLR), and the second sting, within the same year, resulted in large local swelling, wheezing, and chest tightness within 1 to 2 minutes.Case 3The patient was a 57-year-old woman with a history of two episodes of scorpion envenomation. Her initial sting resulted in an LLR, and the subsequent sting 2 years later resulted in an LLR and shortness of breath, abdominal cramps, light-headedness, and a sense of impending doom within 1 hour.Four additional cases included three women and one man, 35 to 48 years old, with histories of LLR (two subjects) and/or neurotoxic symptoms after 1 to 12 scorpion stings each.The group of six control subjects included one woman and five men, 33 to 45 years old, with no history of scorpion stings.METHODSVenom was collected from dissected venom sacs of C. vittatus scorpions captured within Bexar County, Texas. Three microliters of venom was diluted 1:1000 in sterile diluent before filtering (0.22 μm), resulting in approximately 100 μg of venom protein/ml.3Yahel-Niv A Comparative studies in venom obtained from individual scorpions by natural stings.Toxicon. 1979; 17: 435-446Crossref PubMed Scopus (21) Google ScholarSubjects underwent skin prick tests with this 1:1000 diluted venom before titrated intradermal tests (0.02 ml of a 1:1,000,000; advancing by serial 10-fold dilutions to 1:1,000) were performed. Orthogonal wheal and flare diameters were recorded at 15 minutes; and late and delayed tissue induration were measured at 6, 12, 24, and 48 hours. Histamine and diluent controls were used.RESULTSTable I lists responses to venom skin testing. The patient in case 1 had a significantly positive immediate reaction in response to an intradermal test with 1:100,000 diluted venom and a characteristic late-phase response (LPR) with warm, erythematous swelling and surrounding erythema, which were maximal at 8 hours. Concurrent with her positive immediate skin test response, she experienced light-headedness and chest tightness, which resolved spontaneously within approximately 5 minutes. She did not undergo further skin tests. Two remaining patients with systemic reaction and LLR histories and one patient with history of an LLR had firm erythematous indurations after intradermal skin tests with 1:1000 diluted venom. These delayed reactions were maximal at 48 hours and were characteristic of a delayed-type hypersensitivity skin reaction.TABLE ISkin test responsesIntradermal immediateIntradermal late/delayedSubjectHistorical reactionYears since last sting1:1M1:100K1:10K1:10008 hr12hr24 hr48 hrP1Systemic1–+,SymNDND37×45/ 50×65*25×39/ 42×6221×32/ 33×57–P2Sys + LLR7–––––19×2255×60120×125†P3Sys + LLR5–––+––24×2530×38†P4LLR3–––+––23×2825×36† 10×10‡P5LLR2–––+––––P6Minor30–––+––––P7Minor2–––+––––C1NANA–––+–19×24§––C2NANA–––+––––C3NANA++++––––C4NANA––––––––C5NANA–––+––––C6NANA–––+––––Patients (P1 to P7) have a history of a scorpion sting. C1 to C5 are unstung control subjects. Historical reactions included toxic symptoms alone (minor) or toxic symptoms in addition to an LLR or systemic (i.e., anaphylactic) symptoms. Immediate intradermal test results were positive (+) if wheal was greater than 5 mm and erythema was greater than 10 mm in diameter. For P1, systemic symptoms were temporally related to the 11 × 10/26 × 37 (wheal/flare) positive skin test. Late and delayed responses were positive if swelling or induration, as well as associated erythema, was equal to or greater than 10 mm in each orthogonal diameter.Sys, Systemic; ND, not done; NA, not applicable.*Maximal subcutaneous swelling erythema after skin test with 1:100,000 diluted venom.†Maximal erythematous induration after skin test with 1:1000 diluted venom.‡Maximal erythematous induration after skin test with 1:10,000 diluted venom.§Erythema after skin test with 1:1000 diluted venom. Open table in a new tab Nonspecific immediate reactivity was seen in five of six stung patients and five of six unstung control subjects in response to intradermal test with 1:1000 diluted venom. One control subject had a small positive intradermal skin test response to 1:1,000,000 diluted venom (6 × 6 mm wheal and erythema), which did not increase significantly in size with subsequent skin testing and had no associated late reactions.No subject experienced toxic local or systemic symptoms of envenomation during skin testing.DISCUSSIONIn case 1, IgE-mediated hypersensitivity to C. vittatus envenomation was suggested by the patient's history of a systemic reaction, positive intradermal skin test response to 1:100,000 venom dilution, immediate systemic symptoms, and LPR 8 hours after skin testing. Despite a history of systemic reactions to field stings 7 and 5 years before, the patients in cases 2 and 3 demonstrated no immediate response to intradermal skin testing with venom. This lack of response may represent loss of IgE hypersensitivity with time, as has been suggested with other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar The isolated delayed reactions manifested by the patients in cases 2 and 3 and one other stung subject suggest a second immunologic response to scorpion venom—a type IV delayed hypersensitivity reaction, with maximal skin test induration observed at 48 hours. Each of these three patients had reported an LLR with envenomation. Characterization of delayed reactions to scorpion venom will require skin biopsy and analysis of the cellular infiltration during delayed reactions.Patient responses to skin testing with scorpion venom were similar to the clinical experience with skin testing to other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 5Hunt KJ Valentine MD Sobotka AK Lichtenstein LM Diagnosis of allergy to stinging insects by skin testing with hymenoptera venoms.Ann Intern Med. 1976; 85: 56-57Crossref PubMed Scopus (116) Google Scholar Nonspecific skin test responses were seen in 10 (five stung and five unstung) of 12 subjects (83%) intradermally skin tested with scorpion venom diluted 1:1000 (an estimated 100 μg protein/ml). This threshold for nonspecific reactivity is slightly higher than that for Hymenoptera venom, for which a 25% nonspecific skin test rate is reported at 10 μg/ml.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google ScholarOur one control subject with immediate scorpion skin test reactivity but no sting history might have been stung unknowingly. Alternatively, because of this subject's extensive exposure to flying Hymenoptera and imported fire ant stings, we speculate that his positive skin test responses might represent cross-reactivity with other venoms. Further investigation is required to confirm this possibility.In summary, scorpion venom contains antigenic and potentially allergenic proteins. In addition to well-known toxic responses to scorpion envenomation, some individuals may exhibit immunologically mediated responses to envenomation. Among the patients we have studied, immediate and delayed hypersensitivity to the sting of the C. vittatus scorpion may play an important role in the morbidity of scorpion envenomation. As one of 40 species inhabiting the United States, the common Texas striped scorpion, Centruroides vittatus, produces a low toxicity venom,1Keegan HL Lockwood WR Secretory epithelium in venom glands of two species of scorpions of the genus Centruroides marx.Am J Trop Med Hyg. 1971; 20: 770-785PubMed Google Scholar which usually causes immediate sharp pain and local swelling after a sting. Venom neurotoxins may also produce skeletal muscle spasms and paresthesias, particularly of the sting site, face, and tongue.2Rochat H Scorpion toxin and mode of action.Adv Cytopharmacol. 1979; 3: 325-334PubMed Google Scholar Immunologic reactions to envenomation have not been well documented. CASE REPORTSSeven patients with a history of C. vittatus envenomation and six control subjects were evaluated by prick and intradermal skin testing with C. vittatus venom. Three subjects had a history of immediate anaphylactic reactions to envenomation.Case 1The patient was a 38-year-old woman with a history of five episodes of scorpion envenomation. Each of the three most recent episodes, which occurred within a single 30-day period, resulted in immediate local pain, which was followed in minutes by regional paresthesias, chest tightness, wheezing, nausea, vomiting, dizziness, and light-headedness.Case 2The patient was a 53-year-old woman with a history of two episodes of scorpion envenomation. The first sting resulted in a large local reaction (LLR), and the second sting, within the same year, resulted in large local swelling, wheezing, and chest tightness within 1 to 2 minutes.Case 3The patient was a 57-year-old woman with a history of two episodes of scorpion envenomation. Her initial sting resulted in an LLR, and the subsequent sting 2 years later resulted in an LLR and shortness of breath, abdominal cramps, light-headedness, and a sense of impending doom within 1 hour.Four additional cases included three women and one man, 35 to 48 years old, with histories of LLR (two subjects) and/or neurotoxic symptoms after 1 to 12 scorpion stings each.The group of six control subjects included one woman and five men, 33 to 45 years old, with no history of scorpion stings. Seven patients with a history of C. vittatus envenomation and six control subjects were evaluated by prick and intradermal skin testing with C. vittatus venom. Three subjects had a history of immediate anaphylactic reactions to envenomation. Case 1The patient was a 38-year-old woman with a history of five episodes of scorpion envenomation. Each of the three most recent episodes, which occurred within a single 30-day period, resulted in immediate local pain, which was followed in minutes by regional paresthesias, chest tightness, wheezing, nausea, vomiting, dizziness, and light-headedness. The patient was a 38-year-old woman with a history of five episodes of scorpion envenomation. Each of the three most recent episodes, which occurred within a single 30-day period, resulted in immediate local pain, which was followed in minutes by regional paresthesias, chest tightness, wheezing, nausea, vomiting, dizziness, and light-headedness. Case 2The patient was a 53-year-old woman with a history of two episodes of scorpion envenomation. The first sting resulted in a large local reaction (LLR), and the second sting, within the same year, resulted in large local swelling, wheezing, and chest tightness within 1 to 2 minutes. The patient was a 53-year-old woman with a history of two episodes of scorpion envenomation. The first sting resulted in a large local reaction (LLR), and the second sting, within the same year, resulted in large local swelling, wheezing, and chest tightness within 1 to 2 minutes. Case 3The patient was a 57-year-old woman with a history of two episodes of scorpion envenomation. Her initial sting resulted in an LLR, and the subsequent sting 2 years later resulted in an LLR and shortness of breath, abdominal cramps, light-headedness, and a sense of impending doom within 1 hour.Four additional cases included three women and one man, 35 to 48 years old, with histories of LLR (two subjects) and/or neurotoxic symptoms after 1 to 12 scorpion stings each.The group of six control subjects included one woman and five men, 33 to 45 years old, with no history of scorpion stings. The patient was a 57-year-old woman with a history of two episodes of scorpion envenomation. Her initial sting resulted in an LLR, and the subsequent sting 2 years later resulted in an LLR and shortness of breath, abdominal cramps, light-headedness, and a sense of impending doom within 1 hour. Four additional cases included three women and one man, 35 to 48 years old, with histories of LLR (two subjects) and/or neurotoxic symptoms after 1 to 12 scorpion stings each. The group of six control subjects included one woman and five men, 33 to 45 years old, with no history of scorpion stings. METHODSVenom was collected from dissected venom sacs of C. vittatus scorpions captured within Bexar County, Texas. Three microliters of venom was diluted 1:1000 in sterile diluent before filtering (0.22 μm), resulting in approximately 100 μg of venom protein/ml.3Yahel-Niv A Comparative studies in venom obtained from individual scorpions by natural stings.Toxicon. 1979; 17: 435-446Crossref PubMed Scopus (21) Google ScholarSubjects underwent skin prick tests with this 1:1000 diluted venom before titrated intradermal tests (0.02 ml of a 1:1,000,000; advancing by serial 10-fold dilutions to 1:1,000) were performed. Orthogonal wheal and flare diameters were recorded at 15 minutes; and late and delayed tissue induration were measured at 6, 12, 24, and 48 hours. Histamine and diluent controls were used. Venom was collected from dissected venom sacs of C. vittatus scorpions captured within Bexar County, Texas. Three microliters of venom was diluted 1:1000 in sterile diluent before filtering (0.22 μm), resulting in approximately 100 μg of venom protein/ml.3Yahel-Niv A Comparative studies in venom obtained from individual scorpions by natural stings.Toxicon. 1979; 17: 435-446Crossref PubMed Scopus (21) Google Scholar Subjects underwent skin prick tests with this 1:1000 diluted venom before titrated intradermal tests (0.02 ml of a 1:1,000,000; advancing by serial 10-fold dilutions to 1:1,000) were performed. Orthogonal wheal and flare diameters were recorded at 15 minutes; and late and delayed tissue induration were measured at 6, 12, 24, and 48 hours. Histamine and diluent controls were used. RESULTSTable I lists responses to venom skin testing. The patient in case 1 had a significantly positive immediate reaction in response to an intradermal test with 1:100,000 diluted venom and a characteristic late-phase response (LPR) with warm, erythematous swelling and surrounding erythema, which were maximal at 8 hours. Concurrent with her positive immediate skin test response, she experienced light-headedness and chest tightness, which resolved spontaneously within approximately 5 minutes. She did not undergo further skin tests. Two remaining patients with systemic reaction and LLR histories and one patient with history of an LLR had firm erythematous indurations after intradermal skin tests with 1:1000 diluted venom. These delayed reactions were maximal at 48 hours and were characteristic of a delayed-type hypersensitivity skin reaction.TABLE ISkin test responsesIntradermal immediateIntradermal late/delayedSubjectHistorical reactionYears since last sting1:1M1:100K1:10K1:10008 hr12hr24 hr48 hrP1Systemic1–+,SymNDND37×45/ 50×65*25×39/ 42×6221×32/ 33×57–P2Sys + LLR7–––––19×2255×60120×125†P3Sys + LLR5–––+––24×2530×38†P4LLR3–––+––23×2825×36† 10×10‡P5LLR2–––+––––P6Minor30–––+––––P7Minor2–––+––––C1NANA–––+–19×24§––C2NANA–––+––––C3NANA++++––––C4NANA––––––––C5NANA–––+––––C6NANA–––+––––Patients (P1 to P7) have a history of a scorpion sting. C1 to C5 are unstung control subjects. Historical reactions included toxic symptoms alone (minor) or toxic symptoms in addition to an LLR or systemic (i.e., anaphylactic) symptoms. Immediate intradermal test results were positive (+) if wheal was greater than 5 mm and erythema was greater than 10 mm in diameter. For P1, systemic symptoms were temporally related to the 11 × 10/26 × 37 (wheal/flare) positive skin test. Late and delayed responses were positive if swelling or induration, as well as associated erythema, was equal to or greater than 10 mm in each orthogonal diameter.Sys, Systemic; ND, not done; NA, not applicable.*Maximal subcutaneous swelling erythema after skin test with 1:100,000 diluted venom.†Maximal erythematous induration after skin test with 1:1000 diluted venom.‡Maximal erythematous induration after skin test with 1:10,000 diluted venom.§Erythema after skin test with 1:1000 diluted venom. Open table in a new tab Nonspecific immediate reactivity was seen in five of six stung patients and five of six unstung control subjects in response to intradermal test with 1:1000 diluted venom. One control subject had a small positive intradermal skin test response to 1:1,000,000 diluted venom (6 × 6 mm wheal and erythema), which did not increase significantly in size with subsequent skin testing and had no associated late reactions.No subject experienced toxic local or systemic symptoms of envenomation during skin testing. Table I lists responses to venom skin testing. The patient in case 1 had a significantly positive immediate reaction in response to an intradermal test with 1:100,000 diluted venom and a characteristic late-phase response (LPR) with warm, erythematous swelling and surrounding erythema, which were maximal at 8 hours. Concurrent with her positive immediate skin test response, she experienced light-headedness and chest tightness, which resolved spontaneously within approximately 5 minutes. She did not undergo further skin tests. Two remaining patients with systemic reaction and LLR histories and one patient with history of an LLR had firm erythematous indurations after intradermal skin tests with 1:1000 diluted venom. These delayed reactions were maximal at 48 hours and were characteristic of a delayed-type hypersensitivity skin reaction. Patients (P1 to P7) have a history of a scorpion sting. C1 to C5 are unstung control subjects. Historical reactions included toxic symptoms alone (minor) or toxic symptoms in addition to an LLR or systemic (i.e., anaphylactic) symptoms. Immediate intradermal test results were positive (+) if wheal was greater than 5 mm and erythema was greater than 10 mm in diameter. For P1, systemic symptoms were temporally related to the 11 × 10/26 × 37 (wheal/flare) positive skin test. Late and delayed responses were positive if swelling or induration, as well as associated erythema, was equal to or greater than 10 mm in each orthogonal diameter. Sys, Systemic; ND, not done; NA, not applicable. *Maximal subcutaneous swelling erythema after skin test with 1:100,000 diluted venom. †Maximal erythematous induration after skin test with 1:1000 diluted venom. ‡Maximal erythematous induration after skin test with 1:10,000 diluted venom. §Erythema after skin test with 1:1000 diluted venom. Nonspecific immediate reactivity was seen in five of six stung patients and five of six unstung control subjects in response to intradermal test with 1:1000 diluted venom. One control subject had a small positive intradermal skin test response to 1:1,000,000 diluted venom (6 × 6 mm wheal and erythema), which did not increase significantly in size with subsequent skin testing and had no associated late reactions. No subject experienced toxic local or systemic symptoms of envenomation during skin testing. DISCUSSIONIn case 1, IgE-mediated hypersensitivity to C. vittatus envenomation was suggested by the patient's history of a systemic reaction, positive intradermal skin test response to 1:100,000 venom dilution, immediate systemic symptoms, and LPR 8 hours after skin testing. Despite a history of systemic reactions to field stings 7 and 5 years before, the patients in cases 2 and 3 demonstrated no immediate response to intradermal skin testing with venom. This lack of response may represent loss of IgE hypersensitivity with time, as has been suggested with other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar The isolated delayed reactions manifested by the patients in cases 2 and 3 and one other stung subject suggest a second immunologic response to scorpion venom—a type IV delayed hypersensitivity reaction, with maximal skin test induration observed at 48 hours. Each of these three patients had reported an LLR with envenomation. Characterization of delayed reactions to scorpion venom will require skin biopsy and analysis of the cellular infiltration during delayed reactions.Patient responses to skin testing with scorpion venom were similar to the clinical experience with skin testing to other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 5Hunt KJ Valentine MD Sobotka AK Lichtenstein LM Diagnosis of allergy to stinging insects by skin testing with hymenoptera venoms.Ann Intern Med. 1976; 85: 56-57Crossref PubMed Scopus (116) Google Scholar Nonspecific skin test responses were seen in 10 (five stung and five unstung) of 12 subjects (83%) intradermally skin tested with scorpion venom diluted 1:1000 (an estimated 100 μg protein/ml). This threshold for nonspecific reactivity is slightly higher than that for Hymenoptera venom, for which a 25% nonspecific skin test rate is reported at 10 μg/ml.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google ScholarOur one control subject with immediate scorpion skin test reactivity but no sting history might have been stung unknowingly. Alternatively, because of this subject's extensive exposure to flying Hymenoptera and imported fire ant stings, we speculate that his positive skin test responses might represent cross-reactivity with other venoms. Further investigation is required to confirm this possibility.In summary, scorpion venom contains antigenic and potentially allergenic proteins. In addition to well-known toxic responses to scorpion envenomation, some individuals may exhibit immunologically mediated responses to envenomation. Among the patients we have studied, immediate and delayed hypersensitivity to the sting of the C. vittatus scorpion may play an important role in the morbidity of scorpion envenomation. In case 1, IgE-mediated hypersensitivity to C. vittatus envenomation was suggested by the patient's history of a systemic reaction, positive intradermal skin test response to 1:100,000 venom dilution, immediate systemic symptoms, and LPR 8 hours after skin testing. Despite a history of systemic reactions to field stings 7 and 5 years before, the patients in cases 2 and 3 demonstrated no immediate response to intradermal skin testing with venom. This lack of response may represent loss of IgE hypersensitivity with time, as has been suggested with other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar The isolated delayed reactions manifested by the patients in cases 2 and 3 and one other stung subject suggest a second immunologic response to scorpion venom—a type IV delayed hypersensitivity reaction, with maximal skin test induration observed at 48 hours. Each of these three patients had reported an LLR with envenomation. Characterization of delayed reactions to scorpion venom will require skin biopsy and analysis of the cellular infiltration during delayed reactions. Patient responses to skin testing with scorpion venom were similar to the clinical experience with skin testing to other venoms.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 5Hunt KJ Valentine MD Sobotka AK Lichtenstein LM Diagnosis of allergy to stinging insects by skin testing with hymenoptera venoms.Ann Intern Med. 1976; 85: 56-57Crossref PubMed Scopus (116) Google Scholar Nonspecific skin test responses were seen in 10 (five stung and five unstung) of 12 subjects (83%) intradermally skin tested with scorpion venom diluted 1:1000 (an estimated 100 μg protein/ml). This threshold for nonspecific reactivity is slightly higher than that for Hymenoptera venom, for which a 25% nonspecific skin test rate is reported at 10 μg/ml.4Georgitis JW Reisman RE Venom skin tests in insect-allergic and insect-nonallergic populations.J ALLERGY CLIN IMMUNOL. 1985; 76: 803-807Abstract Full Text PDF PubMed Scopus (68) Google Scholar Our one control subject with immediate scorpion skin test reactivity but no sting history might have been stung unknowingly. Alternatively, because of this subject's extensive exposure to flying Hymenoptera and imported fire ant stings, we speculate that his positive skin test responses might represent cross-reactivity with other venoms. Further investigation is required to confirm this possibility. In summary, scorpion venom contains antigenic and potentially allergenic proteins. In addition to well-known toxic responses to scorpion envenomation, some individuals may exhibit immunologically mediated responses to envenomation. Among the patients we have studied, immediate and delayed hypersensitivity to the sting of the C. vittatus scorpion may play an important role in the morbidity of scorpion envenomation.