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LONOMIA CATERPILLAR

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Caterpillars belonging to the Lonomia genus can produce hemostatic disorders that can result in consumptive blood incoagulability and severe hemorrhage. Envenomations by the L. obliqua caterpillar have reached epidemic portions in Brazil.
    B) This management is limited to the Lonomia genus only. For further information on other moths and butterflies or their larval stage, please see the LEPIDOPTERISM management.

Specific Substances

    1) Lonomia achelous (Cramer)
    2) Lonomia obliqua (Walker)

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) TOXICOLOGY: Venom is contained in the hollow spines and skin of the caterpillars. The spines are sharp and break easily when touched, depositing venom in microscopic lesions in the victims' skin. Envenomation can cause severe hemorrhagic syndrome. It appears that the venom in both species contain a fibrinolytic proteases and clotting activators that can produce consumptive coagulopathies, hemorrhagic syndrome and acute renal failure. However, venom from the L. obliqua bristle extract appears to contain both blood coagulation and fibrinolysis factors, but predominantly activates blood coagulation. L. achelous venom is predominantly a fibrinolytic agent.
    B) EPIDEMIOLOGY: The genus lonomia includes 26 species, but only the L. obliqua and L. achelous can cause severe hemorrhagic syndrome. South American Lonomia saturniid moth caterpillars (L. achelous and L. obliqua) are large communal feeding caterpillars. Contact often involves exposure to multiple caterpillars and may produce severe envenomation. They can be found in South America from Venezuela to northern Argentina. Inadvertent exposure to L. obliqua has reached epidemic portions in southern Brazil, and L. achelous envenomations have been reported in the Amazon region.
    C) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: INITIAL: Localized burning and pain after contact with the hairs of the Lonomia species, which is followed by systemic symptoms including headache, fever, vomiting and asthenia several hours after exposure. Consumptive coagulopathy begins as ecchymoses, followed by hematuria, pulmonary hemorrhage, intracerebral hemorrhage and acute renal failure. ONSET: The hemorrhagic phenomena associated with the Lonomia obliqua can occur within 12 to 24 hours following contact. SEVERITY: The extent of envenoming is related not only to the number of caterpillars involved, but to the intensity of the exposure.
    2) SEVERE TOXICITY: Severe hemorrhagic syndrome may develop hours to days after envenomation, resulting in intracerebral, pulmonary or peritoneal hemorrhage and can lead to acute renal failure and death (usually from intracranial hemorrhage). ONSET: The hemorrhagic phenomena associated with the Lonomia obliqua can occur within 12 to 24 hours following contact. SEVERITY: The extent of envenomation is related not only to the number of caterpillars involved, but to the intensity of the exposure. FATALITY RATE: Approximately 2.5%.
    0.2.20) REPRODUCTIVE
    A) Limited data. A 37-week pregnant woman developed hemorrhagic syndrome and acute renal failure after exposure to Lonomia caterpillars, along with genital bleeding. She delivered a healthy baby within 24 hours and recovered completely following supportive care including hemodialysis.

Laboratory Monitoring

    A) Obtain CBC, coagulation (PT/INR, aPTT, thrombin time, platelet count, fibrinogen and D-dimer) and clotting factors (V, VII, IX, X, XI, XIII).
    B) Monitor for clinical evidence of bleeding.
    C) Monitor urinalysis. Hemorrhagic manifestations may include hematuria.
    D) Monitor urine output and renal function.
    E) Monitor neuro function. CT of the head is indicated in all patients with suspected intracranial hemorrhage, mental status depression, or abnormal neurologic exam.

Treatment Overview

    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Patient's with suspected envenomations require immediate evaluation to rule out hemorrhagic syndrome. Early symptoms usually include pain and burning at the site followed by ecchymosis, hematomas, epistaxis, gingival bleeding and hematemesis several hours later. Monitor coagulation and clotting factors. Potential severe bleeding disorders may occur within 12 to 24 hours after exposure.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Severe toxicity can result in bleeding associated with intracranial, pulmonary or peritoneal bleeding that can lead to acute renal failure and death. If available, early use of antivenom is indicated. Treatment should be focused on immediate restoration of clotting factors with human fibrinogen or cryoprecipitate infusions. Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) should also be started.
    3) DECONTAMINATION
    a) PREHOSPITAL: Remove visible bristles with tweezers, wash exposed skin with soap and water.
    b) HOSPITAL: The exposed area should be gently cleansed with running water and carefully inspected to remove any remaining bristles.
    4) AIRWAY MANAGEMENT
    a) Some patients may present comatose due to intracranial hemorrhage; airway management is indicated in patients unable to protect their airway.
    5) ANTIVENOM
    a) A Brazilian antivenom (SALon) has been shown to be clinically effective in treating hemorrhagic syndrome. Usual dose is 5 to 15 vials. It is not available in the US.
    6) HEMOSTATIC AGENTS
    a) Antifibrinolytic agents (eg, aminocaproic acid, tranexamic acid, aprotinin) have been used in Brazil to treat patients with rapid improvement in clinical status and normalization of hemostatic parameters. (NOTE: Aprotinin was withdrawn from the market and is only available for limited use in the United States). Aminocaproic Acid: Adult: Initial dose: 20 grams/day IV (preferred) or oral or tranexamic acid 15 g/day IV (preferred) or oral; Children: Initial dose: 25 mg/kg every 8 hours IV (preferred) or oral or tranexamic acid 15 mg/kg IV (preferred) or oral.
    7) FIBRINOGEN
    a) Based on limited data, it has been suggested that patients treated with human fibrinogen or cryoprecipitate stopped bleeding within a few hours and rapidly improved. FIBRINOGEN: If fibrinogen level is below 100 g/L give human fibrinogen: Adult: Initial dose: 2 g; Children: Initial dose: 1 g. Further doses are dependent on fibrinogen levels.
    8) CRYOPRECIPITATE
    a) Give cryoprecipitate if human fibrinogen is not available; use 4 to 8 units of cryoprecipitate over 24 hours.
    9) PATIENT DISPOSITION
    a) HOME CRITERIA: Not indicated; a patient should be evaluated in a healthcare facility, if lonomia envenomation is suspected.
    b) OBSERVATION CRITERIA: All patients should be observed for 12 to 24 hours following envenomation with serial monitoring of hemostatic parameters.
    c) ADMISSION CRITERIA: Patients with evidence of blood coagulation disorders should be admitted and require intensive therapy and monitoring.

Range Of Toxicity

    A) TOXICITY: Deaths have been reported following a severe envenomation by a single Lonomia caterpillar (L. obliqua and L. achelous) due to bleeding complications from fibrinolysis and coagulation disorders.

Clinical Effects

Summary Of Exposure

    A) TOXICOLOGY: Venom is contained in the hollow spines and skin of the caterpillars. The spines are sharp and break easily when touched, depositing venom in microscopic lesions in the victims' skin. Envenomation can cause severe hemorrhagic syndrome. It appears that the venom in both species contain a fibrinolytic proteases and clotting activators that can produce consumptive coagulopathies, hemorrhagic syndrome and acute renal failure. However, venom from the L. obliqua bristle extract appears to contain both blood coagulation and fibrinolysis factors, but predominantly activates blood coagulation. L. achelous venom is predominantly a fibrinolytic agent.
    B) EPIDEMIOLOGY: The genus lonomia includes 26 species, but only the L. obliqua and L. achelous can cause severe hemorrhagic syndrome. South American Lonomia saturniid moth caterpillars (L. achelous and L. obliqua) are large communal feeding caterpillars. Contact often involves exposure to multiple caterpillars and may produce severe envenomation. They can be found in South America from Venezuela to northern Argentina. Inadvertent exposure to L. obliqua has reached epidemic portions in southern Brazil, and L. achelous envenomations have been reported in the Amazon region.
    C) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: INITIAL: Localized burning and pain after contact with the hairs of the Lonomia species, which is followed by systemic symptoms including headache, fever, vomiting and asthenia several hours after exposure. Consumptive coagulopathy begins as ecchymoses, followed by hematuria, pulmonary hemorrhage, intracerebral hemorrhage and acute renal failure. ONSET: The hemorrhagic phenomena associated with the Lonomia obliqua can occur within 12 to 24 hours following contact. SEVERITY: The extent of envenoming is related not only to the number of caterpillars involved, but to the intensity of the exposure.
    2) SEVERE TOXICITY: Severe hemorrhagic syndrome may develop hours to days after envenomation, resulting in intracerebral, pulmonary or peritoneal hemorrhage and can lead to acute renal failure and death (usually from intracranial hemorrhage). ONSET: The hemorrhagic phenomena associated with the Lonomia obliqua can occur within 12 to 24 hours following contact. SEVERITY: The extent of envenomation is related not only to the number of caterpillars involved, but to the intensity of the exposure. FATALITY RATE: Approximately 2.5%.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Dyspnea was an early symptom of lonomia obliqua exposure in a pregnant woman (Fan et al, 1998).
    B) PULMONARY HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Pulmonary hemorrhage has been associated with severe envenomation (Kowacs et al, 2006).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Frontal headache has been reported as an early symptom of lonomia envenomation (Fan et al, 1998).
    B) CEREBRAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 52-year-old woman came in contact with a L. obliqua and felt immediate burning at the site followed by 2 days of generalized ecchymosis and bruising at the site, along with nausea and vomiting. On admission the patient was unconscious with a Glasgow coma score of 10 and Cheyne-Stokes breathing. Clotting factors were abnormal. A CT of the brain showed an intracerebral hematoma in the right parieto-occipital region and she died 2 days later (Duarte et al, 1996)
    b) CASE REPORT - A 70-year-old woman presented in coma with a 4-day history of a severe bleeding diathesis characterized by several skin hemorrhages and hematuria after touching a Lonomia oblique caterpillar. She died 7 days after envenomation from multiple intracerebral hemorrhages (Kowacs et al, 2006).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting are early findings following envenomation. Abdominal pain has also been reported (Gamborgi et al, 2006; Fan et al, 1998; Duarte et al, 1996).
    B) GASTROINTESTINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Hemorrhage is characteristic finding of lonomia envenoming. Effects associated with spontaneous gastrointestinal bleeding have included: gum bleeding, epistaxis, hematemesis and melena (Diaz, 2005; Fan et al, 1998).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES - In a cohort study conducted between 1989 and 2003, patient outcome was evaluated to determine the efficacy of antivenom (SALon therapy became available in 1995), as compared to supportive care following envenomation by caterpillars of the Lonomia obliqua species. Of the 2067 cases, 39 (1.9%) patients developed acute renal failure (ARF) (creatinine value greater than 1.5 mg/dL with no history of renal disease) with seven deaths reported during the period prior to SALon therapy. The primary factor associated with the development of acute renal failure was that patients who became severely ill had contact with a larger number of caterpillars as compared to other patients. These patients were also more likely to have blood coagulation abnormalities, more complaints of systemic symptoms, and evidence of gross hematuria (100%) and proteinuria (87%). Four patients developed chronic renal failure (Gamborgi et al, 2006).
    b) RISK FACTOR - Patients usually present with worse bleeding, prior to the onset of acute renal failure (Gamborgi et al, 2006).
    c) INCIDENCE - Approximately 2% of exposures, even with the introduction of antivenom (Gamborgi et al, 2006).
    d) CASE REPORT - A 37 year-old, 37-week, pregnant woman inadvertently came in contact with Lonomia obliqua caterpillars on her arm and within a few minutes developed a severe headache, nausea, vomiting, and dyspnea. Bleeding of the gums and anuria were also noted within several hours of exposure. Approximately 24 hours after exposure, she developed genital bleeding and delivered a healthy infant. The patient's hospital course was complicated by post delivery hemorrhage, hypovolemic shock, and acute renal failure. Renal function returned to normal by day 36, after receiving supportive care and hemodialysis for 3 weeks (Fan et al, 1998). The authors suggested that abruptio placentae may have occurred in this patient due to bleeding into the placenta.
    B) HEMATURIA SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Hematuria has been reported following envenoming by lonomia caterpillars (Gamborgi et al, 2006; Kowacs et al, 2006; Arocha-Pinango & Guerrero, 2003).
    b) CASE REPORT - A 70-year-old woman presented in coma with a 4-day history of a severe bleeding diathesis characterized by several skin hemorrhages and hematuria after touching a L. oblique caterpillar. She died 7 days after envenomation from multiple intracerebral hemorrhages (Kowacs et al, 2006).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMORRHAGE
    1) Ecchymosis is an early finding followed by bleeding at multiple sites, which can progress to intracerebral, peritoneal or pulmonary hemorrhage after a severe envenomation (Arocha-Pinango & Guerrero, 2003; Duarte et al, 1996).
    B) BLOOD COAGULATION PATHWAY FINDING
    1) WITH POISONING/EXPOSURE
    a) Acquired hemorrhagic syndrome was reported in 6 patients following exposure to the Lonomia species. Low levels of fibrinogen, factor V, factor XIII, protein C, plasminogen, and alpha-2 antiplasmin were recorded in all 6 cases. Massive fibrinolysis followed (as demonstrated by in vitro experiments), which may have resulted from prolonged low levels of factor XIII (Kelen et al, 1995).
    1) Saturniidae moth caterpillars may produce a prolonged fibrinolytic bleeding disorder. Deaths have occurred. A stable basic fibrinolysin is contained in the hemolymph, saliva, and hair secretions (Burnett et al, 1986).
    2) It has been observed that the primary cause of bleeding complications following a L. obliqua envenomation is due to a consumptive coagulopathy that can be induced by the presence of procoagulant proteins. In contrast, coagulopathies in Lonomia achelous envenomations are likely due to the direct activation of the fibrinolytic system (Fritzen et al, 2003).
    3) CASE SERIES - In a study of 105 patients with hemorrhagic syndrome due to contact with Lonomia obliqua caterpillar, prolonged coagulation was observed in most cases, which was primarily due to consumptive coagulopathy and secondary fibrinolysis (Zannin et al, 2003a).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) SKIN FINDING
    1) WITH POISONING/EXPOSURE
    a) Local symptoms of envenoming may often include initial burning pain at the site, along with possible numbness and pruritus (Diaz, 2005; Gamborgi et al, 2006).
    B) ECCHYMOSIS
    1) WITH POISONING/EXPOSURE
    a) Localized ecchymosis may occur following contact with the hairs of lonomia caterpillars (Diaz, 2005; Duarte et al, 1996). This can be followed by generalized ecchymoses and bleeding from the site, along with spontaneous bleeding from mucous membranes and other sites (Diaz, 2005).

Reproductive

    3.20.1) SUMMARY
    A) Limited data. A 37-week pregnant woman developed hemorrhagic syndrome and acute renal failure after exposure to Lonomia caterpillars, along with genital bleeding. She delivered a healthy baby within 24 hours and recovered completely following supportive care including hemodialysis.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of the venom found in the lonomia caterpillar.
    3.20.3) EFFECTS IN PREGNANCY
    A) ABRUPTIO PLACENTA
    1) CASE REPORT - A 37 year-old, 37-week, pregnant woman inadvertently came in contact with Lonomia obliqua caterpillars on her arm and within a few minutes developed a severe headache, nausea, vomiting, and dyspnea. . Bleeding of the gums and anuria was also noted within several hours of exposure. Approximately 24 hours after exposure the patient developed genital bleeding and was thought to have abruptio placentae. An infant was born slightly hypoxic, but was discharged to home within 2 days. The patient's course was complicated by post delivery hemorrhage, hypovolemic shock, and acute renal failure. Following supportive care including hemodialysis for 3 weeks, renal function returned to normal by day 36 (Fan et al, 1998). The authors suggested that abruptio placentae may have occurred in this patient due to bleeding into the placenta.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects or risk to a nursing infant following maternal exposure.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain CBC, coagulation (PT/INR, aPTT, thrombin time, platelet count, fibrinogen and D-dimer) and clotting factors (V, VII, IX, X, XI, XIII).
    B) Monitor for clinical evidence of bleeding.
    C) Monitor urinalysis. Hemorrhagic manifestations may include hematuria.
    D) Monitor urine output and renal function.
    E) Monitor neuro function. CT of the head is indicated in all patients with suspected intracranial hemorrhage, mental status depression, or abnormal neurologic exam.
    4.1.2) SERUM/BLOOD
    A) Monitor CBC, coagulation and clotting factors in all suspected cases. Monitor closely and obtain serial tests as indicated.
    1) L. OBLIQUA: The hemorrhagic syndrome that may occur following envenomation by a L. obliqua caterpillar is a result of consumption coagulopathy and secondary fibrinolysis. Laboratory findings may typically include: a normal or slightly low platelet count, anemia, prolonged prothrombin time (PT), as well as a decrease in fibrinogen, plasminogen, Factor V and Factor XIII levels associated with an increase in fibrin degradation products (Kowacs et al, 2006; Fan et al, 1998).
    2) L. ACHELOUS: The venom causes fibrinolysis (Carrijo-Carvalho & Chudzinski-Tavassi, 2007). The bleeding syndrome associated with this venom is likely to produce a decrease in fibrinogen, factor XIII, plasminogen, and factor V with a normal platelet count (Lopez et al, 2000).
    B) Monitor renal function. Acute renal failure has been reported in the literature following L. obliqua envenomation.
    4.1.3) URINE
    A) Monitor urine output. Hemorrhagic manifestations may include hematuria.
    4.1.4) OTHER
    A) OTHER
    1) CT HEAD
    a) CT of the head is indicated in all patients with suspected intracranial hemorrhage, depressed mental status or abnormal neurologic exam.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.1) ADMISSION CRITERIA/DERMAL
    A) Patients with evidence of blood coagulation disorders should be admitted and require intensive therapy and monitoring.
    6.3.5.2) HOME CRITERIA/DERMAL
    A) Not indicated; a patient should be evaluated in a healthcare facility, if lonomia envenomation is suspected.
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) All patients should be observed for at least 12 to 24 hours following envenomation with serial monitoring of hemostatic parameters.

Monitoring

    A) Obtain CBC, coagulation (PT/INR, aPTT, thrombin time, platelet count, fibrinogen and D-dimer) and clotting factors (V, VII, IX, X, XI, XIII).
    B) Monitor for clinical evidence of bleeding.
    C) Monitor urinalysis. Hemorrhagic manifestations may include hematuria.
    D) Monitor urine output and renal function.
    E) Monitor neuro function. CT of the head is indicated in all patients with suspected intracranial hemorrhage, mental status depression, or abnormal neurologic exam.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Remove visible bristles with tweezers, wash exposed skin with soap and water.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Oral exposure unlikey; see DERMAL section.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) Avoid scratching and rubbing the site because of the potential risk of causing the hairs to penetrate deeper into the skin. The first treatment should be washing the spicules out with running water.
    6.9.2) TREATMENT
    A) BLOOD COAGULATION DISORDER
    1) GENERAL
    a) Treatment should be focused on immediate restoration of hemostatic parameters including clotting factors with human fibrinogen or cryoprecipitate infusions. Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) should also be started. Continuous monitoring of clotting status should be performed (Diaz, 2005). Some authors suggest that treatment with whole blood or fresh frozen plasma may cause disseminated intravascular coagulation and thrombocytopenia, leading to renal insufficiency and death (Arocha-Pinango & Guerrero, 2003; Kowacs et al, 2006).
    2) ANTIVENOM
    a) Contact with hairs from the species Lonomia may induce a blood incoagulability followed by a massive fibrinolysis. If available, it has been suggested that early treatment with a Brazilian antivenom (SALon from Instituto Butantan) may induce a quicker recovery of fibrinogen levels and reduce the strong fibrinolysis that accompanies defibrinogenation, but it is not available in the US (Caovilla & Barros, 2004; Kelen et al, 1995).
    b) A randomized prospective controlled trial was conducted in order to compare the efficacy of two different doses of antilonomic serum (SALon) for treatment of Lonomia obliqua caterpillar-induced hemorrhagic syndrome. The study involved 44 patients with grade I or II hemorrhagic syndrome randomly assigned to either receive 3 vials of SALon (total dose 10.5 milligrams [group A]) (n=22) or 5 vials of SALon (total dose 17.5 milligrams [group B]) (n=22). Both regimens were diluted in saline solution and administered at an infusion rate of 3 to 5 milliliters/minute. Treatment efficacy was evaluated according to the time necessary for blood coagulation to return to normal, the incidence of adverse reactions, and hospitalization time.
    1) There was no significant difference, between groups A and B, with regards to the time until resolution of blood coagulation (15.3 +/-6.6 hrs (group A ) vs. 19.1 +/- 8 hrs (group B) [p=0.09]), the incidence of adverse effects, or the mean hospitalization time (3.4 +/- 1.0 day (group A) vs. 3.1 +/- 0.8 days (group B) [p=0.35]). Therefore, administration of 3 vials of antilonomic serum appears to be as effective as administration of 5 vials in treating hemorrhagic syndrome induced by dermal contact with L. obliqua caterpillars. It was also noted that the patients in this study presented with less severe bleeding events which may support the early use and efficacy of SALon therapy, as compared to earlier cases reported in the literature of severe hemorrhage (Caovilla & Barros, 2004).
    3) ANTIFIBRINOLYTIC AGENTS
    a) Antifibrinolytic agents such as aminocaproic acid, tranexamic acid and aprotinin have been used in Brazil to treat patients following severe envenomation (Arocha-Pinango & Guerrero, 2003). As suggested by the manufacturer these agents may be useful to enhance hemostasis when fibrinolysis contributes to bleeding (Prod Info AMICAR(R) IV injection, oral solution, oral tablets, 2005). (NOTE: Aprotinin was removed from the US market in May 2008 due to an increased risk of mortality with aprotinin; it is available on a limited basis for investigational use only).
    b) Some authors advocate the administration of antifibrinolytic agents alone or in combination with cryoprecipitate or purified fibrinogen (Arocha-Pinango & Guerrero, 2003; Kowacs et al, 2006). This approach has not been systematically studied.
    1) Currently there is very limited data with this therapy. The following is based on ONLY one study and general manufacturer information:
    1) AMINOCAPROIC ACID: ADULTS aminocaproic acid at 20 grams/day IV (preferred) or oral . CHILDREN: aminocaproic acid 25 mg/kg every 8 hours (Arocha-Pinango & Guerrero, 2003).
    2) For hemorrhage secondary to increased fibrinolysis: the manufacturer suggests: ADULT: Initial dose of 16 to 20 mL (4-5 grams) IV, diluted in 250 mL of D5W or NS, infuse over 1 hour; followed by a continuing infusion at the rate of 4 mL (1 g) per hour in 50 mL of diluent for about 8 hours or until bleeding is controlled. For Oral dosing give: ADULT: 5 grams during the first hour followed by 1 gram/hour orally for 8 hours or until bleeding is controlled (Prod Info AMICAR(R) IV injection, oral solution, oral tablets, 2005).
    3) TRANEXAMIC ACID - Alternative to amiocaproic acid. ADULTS tranexamic acid 15 g/day IV (preferred) or oral. CHILDREN tranexamic acid 15 mg/kg IV (preferred) or oral
    4) APROTININ (may be available in non-US countries): ADULT: Initially give 400,000 units diluted in 500 mL NS over one hour, followed by 200,000 units every 6 hours as an infusion. CHILDREN: Give 30,000 units diluted in 500 mL NS infused over 1 hour, followed by 600 units/kg infused over 6 hours (Arocha-Pinango & Guerrero, 2003).
    4) FIBRINOGEN
    a) It has been suggested that patients treated with human fibrinogen or cryoprecipitate stopped bleeding in a few hours and rapidly improved clinically as well as having normalization of their clotting studies. The following dosing is based on ONLY one study:
    1) ADULTS: If fibrinogen level is below 100 g/L give human fibrinogen 2 g initially then subsequent doses depending on the fibrinogen level (Arocha-Pinango & Guerrero, 2003). The manufacturer suggests that the dose should equal the target level (mg/dL) - measured level (mg/dL) divided by 1.7 (mg/dL per mg/kg body weight). A target fibrinogen level of 100 mg/dL is also suggested until hemostasis is obtained (Prod Info RiaSTAP(TM) lyophilized powder, intravenous injection, 2009).
    2) CHILDREN: Initially 1 g human fibrinogen with further doses dependent on fibrinogen levels (Arocha-Pinango & Guerrero, 2003).
    3) CRYOPRECIPITATE - Give cryoprecipitate if human fibrinogen is not available; use 4 to 8 units of cryoprecipitate over 24 hours (Arocha-Pinango & Guerrero, 2003)
    B) ANAPHYLAXIS
    1) Patient's receiving antivenom (antilonomic (SALon) equine serum) may be at risk to develop anaphylaxis (Caovilla & Barros, 2004).
    2) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    3) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    4) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    5) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    6) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    7) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    8) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    9) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    10) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    11) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    12) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    13) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    C) HYPOTENSIVE EPISODE
    1) Correct hypovolemia, if present. Monitor vital signs and hemostatic parameters. Provide IV fluid replacement as necessary.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Based on limited data, hemodialysis has been used successfully to treat acute renal failure associated with severe hemorrhagic syndrome (Fan et al, 1998).

Range Of Toxicity

Summary

    A) TOXICITY: Deaths have been reported following a severe envenomation by a single Lonomia caterpillar (L. obliqua and L. achelous) due to bleeding complications from fibrinolysis and coagulation disorders.

Minimum Lethal Exposure

    A) GENERAL: Deaths have been reported following a severe envenomation by a single Lonomia. Inadvertent exposure can occur after the venom enters the skin through microscopic lesions caused by the spines of the hairy larvae. The venom accumulates in the subcuticular space and at the tip of the spine where the toxin is deposited, which can easily be broken and result in a release of venom. In humans and animals, fibrinolysis and coagulation disorders have been observed and have resulted in death in some cases (Ramos et al, 2004).
    B) CASE REPORT - A 70-year-old woman presented in coma with a 4-day history of a severe bleeding diathesis characterized by several skin hemorrhages and hematuria after touching a Lonomia oblique caterpillar. She died 7 days after envenomation from multiple intracerebral hemorrhages (Kowacs et al, 2006).
    C) CASE REPORT - A 52-year-old woman came in contact with a L. obliqua and felt immediate burning at the site followed by 2 days of generalized ecchymosis and bruising at the site, along with nausea and vomiting. On admission the patient was unconscious with a Glasgow coma score of 10 and Cheyne-Stokes breathing. Clotting factors were abnormal. A CT of the brain showed an intracerebral hematoma in the right parieto-occipital region and she died 2 days later (Duarte et al, 1996).

Maximum Tolerated Exposure

    A) CASE SERIES - In a cohort study conducted between 1989 and 2003, patient outcomes were evaluated to determine the efficacy of antilonomic serum (SALon therapy became available in 1995), as compared to supportive care following envenomation by caterpillars of the Lonomia obliqua species. Of the 2067 cases, 39 (1.9%) patients developed acute renal failure (ARF) (creatinine value greater than 1.5 mg/dL with no history of renal disease) with seven deaths reported during the period prior to SALon therapy. The primary factor associated with the development of acute renal failure was that patients who became ill had contact with a larger number of caterpillars as compared to other patients (Gamborgi et al, 2006).
    B) CASE REPORT - A 37 year-old, 37-week, pregnant woman inadvertently came in contact with Lonomia obliqua caterpillars on her arm and within a few minutes developed a severe headache, nausea, vomiting and dyspnea. Approximately 24 hours after exposure, she developed genital bleeding and delivered a healthy infant. The patient's hospital course was complicated by post delivery hemorrhage, hypovolemic shock and acute renal failure as noted by rising creatinine and potassium concentrations. Renal function returned to normal by day 36, after receiving supportive care and hemodialysis for 3 weeks (Fan et al, 1998).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Contact with the Lonomia obliqua caterpillar bristles can lead to envenoming that is characterized by severe consumption coagulopathy and secondary fibrinolysis. It is thought that these events are triggered by procoagulating agents which include a prothrombin activator and a Factor X activator. Envenomation by the Lonomia achelous caterpillar is more likely to produce blood coagulation disorders by activating the fibrinolysis system.
    B) HUMAN
    1) SUMMARY
    a) Although the clinical presentation resulting in impaired blood coagulation is similar following envenomation, the venoms of L. obliqua and L. achelous appear to trigger different mechanisms of the coagulation system. L. achelous venom appears to predominantly activate the fibrinolysis system, while L. obliqua venom predominantly activates blood coagulation (Carrijo-Carvalho & Chudzinski-Tavassi, 2007).
    2) LONOMIA ACHELOUS
    a) Lonomia achelous venom causes fibrinolysis, likely due to direct and indirect fibrinolytic activities and FXIII inactivator activity. L. achelous venom contains several fibrinolytic compounds Achelase I and Achelase II, which both have plasmin-like activity. It also has procoagulant effects, but it can be masked by its severe fibrinolysis effects (Carrijo-Carvalho & Chudzinski-Tavassi, 2007).
    3) LONOMIA OBLIQUA
    a) Contact with the Lonomia obliqua caterpillar bristles can lead to envenoming that is characterized by severe consumptive coagulopathy and secondary fibrinolysis. It is thought that these events are triggered by procoagulant agents which include a prothrombin activator and a Factor X activator (Reis et al, 2006). The venom accumulates in the subcuticular space and at the tip of the spine (which is an empty tubular passage) where the toxin is stored. If a spine gets broken, it can release venom when touched (Ramos et al, 2004).
    1) In both human and animal studies, fibrinolysis and coagulation disorders have been reported following severe envenomations (Ramos et al, 2004).
    2) In one study, a prothrombin activator called Lopap (Lonomia obliqua prothrombin activator protein), was isolated from the bristles of the L. obliqua caterpillar. This Lopap is a 69 kDa homotetrameric protein that is able to generate thrombin and pre-thrombin-2, by hydrolysing the Arg(284) -Thr(285) peptide bond of the human prothrombin molecule (Reis et al, 2006).
    a) It was noted that recombinant Lopap (rLopap) hydrolyzes prothrombin (at concentration rates similar to human plasma), which can lead to an active thrombin generation that follows linear kinetics. It also has the ability to decrease the recalcification time in normal plasma. Based on these findings the authors concluded that rLopap has proteolytic activity that is similar to native Lopap (Reis et al, 2006).

References

General Bibliography

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