Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application.

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

'Reversible cardiomyopathy' in patients with severe scorpion envenoming by Tityus serrulatus: evolution of enzymatic, electrocardiographic and echocardiographic alterations.

Severe scorpion envenoming is characterized by cardiocirculatory failure which may lead to pulmonary oedema. These are the major causes of death among victims of scorpion stings. Involvement of the heart has been attributed to the massive release of catecholamines and/or to a direct toxic effect of the venom on cardiac fibres, while pulmonary oedema has been considered to be of cardiogenic or non-cardiogenic origin. We present here the clinical, laboratory, electrocardiographic and echocardiographic data of 12 victims of severe Tityus serrulatus stings. These patients had important echocardiographic evidence of moderate to severe left ventricular (LV) dysfunction with diffuse LV hypokinesia and reduced ejection fraction. Seven developed pulmonary oedema. The clinical course of all the patients was satisfactory and the laboratory, electrocardiographic and echocardiographic changes returned to normal, usually within 1 week of the sting. The important alterations detected by echocardiography as early as during the 1st few hours after the sting, taken together with the enzymatic and electrocardiographic data, confirm that LV dysfunction is responsible, either alone or in combination with other factors, for the cardiac insufficiency and pulmonary oedema encountered in scorpion envenoming.

Rhabdomyonecrosis experimentally induced in Wistar rats by Africanized bee venom.

Damage is reported to skeletal muscle experimentally induced in Wistar rats by Africanized bee venom (ABV). Rhabdomyonecrosis was demonstrated indirectly by increased serum levels of the enzymes aspartate-aminotransferase and total creatine kinase, and directly by necrosis and inflammation observed by standard light microscopy of skeletal muscle. To our knowledge, this is the first report of a systemic damaging effect of ABV on skeletal muscle of experimentally envenomated rats. These data appear to reproduce experimentally some of the findings reported in cases of human envenomation due to multiple Africanized bee stings.

[Immediate hypersensitivity reactions after intravenous use of antivenin sera: prognostic value of intradermal sensitivity tests]. / Reações de hipersensibilidade imediatas após uso intravenoso de soros antivenenos: valor prognóstico dos testes de sensibilidade intradérmicos.

The frequency and class of immediate-type hypersensitivity manifestations were studied in 494 snakebitten and scorpion stung patients who were treated with intravenous injections of antivenom sera. These patients were admitted to HC-FMRPUSP from 1983 to 1988. The effectiveness of a hypersensitivity skin test was also investigated. Eighty two out of 320 patients admitted following snake bites (25.6%) had immediate-type reactions consisting of isolated skin lesions (40%), skin lesions plus respiratory manifestations (19%) and gastrointestinal involvement (17%). Anaphylactic shock occurred in ten patients (12%). Thirteen out of 174 patients admitted following scorpion stings had immediate-type reactions (7.5%). There was also a preponderance of skin reactions. Anaphylactic shock was observed in one patient. The positive predictive value of hypersensitivity skin test was 31.8% and its sensibility was 54.8%. These data show that a hypersensitivity skin test is ineffective in predicting immediate-type hypersensitivity manifestations in patients given snake and scorpion antivenom. Considering these results, this test should be eliminated as a routine procedure when treating victims of poisonous animals. These studies indicate that prior to the administration of antivenom anti-histamine (H1- and H2-antagonists) as well corticosteroids should be given by i.v. route in order to prevent or reduce hypersensitivity reactions. Antivenom sera must always be given under continuous medical surveillance by an intravenous route, without dilution, drop by drop for 15-30 minutes.

Acute myocardial infarction-like enzyme profile in human victims of Crotalus durissus terrificus envenoming.

The clinical signs and symptoms of Crotalus durissus terrificus envenoming are due to the neurotoxic, myotoxic systemic and thrombin-like coagulating effects of the venom. The rhabdomyolysis observed after envenoming caused by snakes, the venom of which has a systemic myotoxic activity, has been limited thus far to skeletal muscle, with no reports of myocardial damage. In the present paper we report serial measurements of serum creatine kinase (CK), lactic dehydrogenase (LD) and of CK-MB and LD1 isoenzymes in human victims of Crotalus bites. The results were similar to those reported for acute myocardial infarction even though the clinical evolution, electrocardiogram and echocardiogram findings did not show any involvement of cardiac muscle. The enzymatic profile detected, as well as the pattern of focal involvement observed in muscle biopsies obtained from these patients, suggest that there may be a type of skeletal muscle fibre that is preferentially damaged by C. durissus terrificus venom, i.e., type I and/or IIa fibres, the composition of which is richer in CK-MB and LD1, and is similar to that of cardiac fibres.

Electron-microscopic study of systemic myonecrosis due to poisoning by tropical rattlesnake (Crotalus durissus terrificus) in humans.

This article describes the ultrastructural study of skeletal muscle biopsy specimens from five patients following envenomization by tropical rattlesnake (Crotalus durissus terrificus). All the patients were bitten in the leg and the biopsy specimens were obtained from the contralateral gastrocnemius muscle in the middle of the lower leg. A wide spectrum of detailed ultrastructural changes involving muscle fibers and microvasculature was demonstrated. Essentially, such lesions included widespread necrotic myofibers intermixed with intact fibers, accompanied by changes in the endothelial lining of the intramuscular blood capillaries and small arterial vessels, reducing their lumens. Since these alterations were observed in biopsy specimens from the limb contralateral to the site of the bite, they clearly demonstrate the systemic myonecrotic action of the venom of a tropical rattlesnake. On the basis of these data, the mechanism of venom-induced myopathy is described. It is postulated that the pathogenesis of systemic myonecrosis due to poisoning by C durissus terrificus is a complex one, probably due to direct damage to cells by the myotoxins of the venom, as well as indirect effects due to ischemia.

Clinical and laboratory features of South American rattlesnake (Crotalus durissus terrificus) envenomation in children.

The venom of the South American rattlesnake Crotalus durissus terrificus was first reported to have mainly haemolytic and neurotoxic physiopathological activities. Later studies demonstrated the systemic myotoxic action of the venom, characterized by the release of myoglobin from damaged skeletal muscle into serum and urine, and a recent report ruled out the presence of intravascular haemolysis in 3 patients, one child and 2 adults. The present paper describes the clinical-laboratory evolution of 10 children bitten by C. durissus terrificus; 2 developed acute renal failure and one died. The myotoxic activity of the venom was evaluated by measuring serum lactic dehydrogenase, creatine kinase and aspartate aminotransferase, by detection of myoglobin in serum and urine, and by muscle biopsy. Haemolytic activity was evaluated by serial measurements of serum haemoglobin and haptoglobin and by detection of urine haemoglobin. We conclude that the signs and symptoms exhibited by patients bitten by C. durissus terrificus are due only to the myotoxic and neurotoxic action of the venom. The only patients with major morbidity were those who initially received subcutaneous antivenin and did not receive definitive antivenin therapy until later.

Evidence that Crotalus durissus terrificus (South American rattlesnake) envenomation in humans causes myolysis rather than hemolysis.

The venom of the South American rattlesnake Crotalus durissus terrificus was originally reported to have a pathophysiological activity mainly involving hemolysis and neurotoxicity. The systemic myotoxic action of this venom was demonstrated in 1985. In the present paper we report clinical and laboratory data concerning three patients bitten by C. durissus terrificus and treated at the University Hospital of Ribeirão Preto, University of São Paulo. The normal haptoglobin levels detected in the serum of these patients during the first 48 hr after the accident, as well as the absence of hemoglobin in darkened urine samples as evaluated by immunodiffusion against anti-hemoglobin serum, rule out the occurrence of intravascular hemolysis. These data permit us to conclude that the signs and symptoms observed in human envenomation with C. durissus terrificus are due to a myotoxic and neurotoxic action of the venom.

Myonecrosis, myoglobinuria and acute renal failure induced by South American rattlesnake (Crotalus durissus terrificus) envenomation in Brazil.

The venom of the Brazilian rattlesnake Crotalus durissus terrificus is know to have hemolytic and neurotoxic physiopathological activities which may cause acute renal failure with hemoglobinuria and/or methemoglobinuria. As far as we know, no report has been published on the ability of the venom of this rattlesnake species to cause rhabdomyolysis. In the present paper we demonstrate that the venom of Brazilian snakes of the genus Crotalus can induce systemic myonecrosis. Clinical, laboratory and anatomo-pathological data for two patients referred to the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, 24 hr after a rattlesnake bite, are presented. In both cases, exaggerated elevation of serum levels of the enzymes creatine phosphokinase, lactate dehydrogenase and glutamic-oxaloacetic transaminase were detected, as well as data suggesting acute hypercatabolic renal failure. Immunoelectrophoresis of the serum and urine of these patients, carried out against specific anti-myoglobin serum (Behringwerke), demonstrated myoglobinemia and myoglobinuria, confirming injury to muscle tissue. Electron microscopy of a calf muscle biopsy taken from the leg contralateral to the bite from one patient revealed foci of myonecrosis.