On-line version ISSN 1678-4936
J. Venom. Anim. Toxins vol.8 no.1 Botucatu 2002
1 Faculdade do Norte Paulista, Bebedouro, São Paulo State, Brazil; 2 Magnetic Resonance Unit, University Hospital, Botucatu School of Medicine, UNESP; 3 Department of Tropical Diseases and Imaging Diagnosis, Botucatu School of Medicine - UNESP, São Paulo State, Brazil; 4 Center for the Study of Venoms and Venomous Animals-CEVAP-UNESP, State of São Paulo, Brazil.
ABSTRACT: The objective of this clinical study was to evaluate local tissue damage caused by Bothrops sp envenoming in relation to lesion type and damaged tissues using magnetic resonance imaging (MRI). Fifteen patients bitten by Bothrops snakes were treated at the Emergency Unit of the Tropical Diseases Unit at the University Hospital, Botucatu School of Medicine, UNESP, São Paulo State, Brazil. After receiving specific serotherapy, the patients were submitted to MR of the bite site. T1 spin-echo MRI were obtained revealing the following lesions: edema (n=9), edema associated with hemorrhage (n=5), and hemorrhage (n=1). Perimuscular areas (n=6) and subcutaneous tissues (n=5) were the most affected, followed by muscular tissues (n=4). It is important to mention that MRI did not show myonecrosis of the bite site, a widely reported finding in anatomical and histopathological experimental studies.
KEY WORDS: Bothrops sp, magnetic resonance imaging, tissue damage, hemorrhage, myonecrosis.
INTRODUCTIONEnvenoming caused by Bothrops snakes are a major public health problems due to their incidence, severity, and sequeale (3). Today, 70 to 80% of snake envenomings in São Paulo State are attributed to Bothrops snakes due to their wide distribution and large number of species (3). Bothrops snake venoms are a complex mixture of biological active peptides and proteins (3,20,21), which can cause local and systemic lesions including pain, edema, hemorrhage, tissue necrosis, and blood coagulation disorders (2,4,8,12,14,16). Magnetic resonance imaging (MRI) is used to produce images of body structures. It is based on nuclear magnetism of substances present in biological tissues (8,17). This is a valuable diagnostic tool, as it is non-invasive and shows high spatial resolution in evaluating skeletal muscular structures (17). There is little clinical information about lesions caused by Bothrops sp envenoming using imaging diagnosis (8,9,22). The objective of this study was to evaluate local tissue lesions in patients bitten by Bothrops sp. These were evaluated by MRI in relation to lesion type and damaged tissues on hospital admission and after serotherapy.
PATIENTS AND METHODS
We studied 15 patients (10 male and 5 female) aged between 5 and 68 years, all bitten by Bothrops snakes. Patients received specific treatment at the Emergency Unit (University Hospital, Botucatu School of Medicine UNESP) and were then hospitalized at the Tropical Diseases Unit for additional treatment and clinical follow up. See Table 1 for patient details upon hospital admission.
|Table 1. Patients (P) bitten by Bothrops snakes: age (A), sex (S), time elapsed (hours) between the bite and medical treatment (TT), clinical picture (CP), use of tourniquet (T), bite site (BS), local manifestations (LM), systemic manifestations (SM), number of antivenom vials administered (NV), resonance magnetic (hours) evaluation (RM), tissue damage (TD) and lesion type (LT).|
MRI lesion evaluations of the bite sites were performed after serotherapy, using an imager with a superconductive magnet operating at 0.5 Tesla. Images were obtained in adaxial/axial and coronal slice planes, using spin-echo (SE) sequences at T1 relaxation times. Gadolinium (Gd) intravenous paramagnetic contrast was used (0.2 ml/kg) in T1 images. Lesion types and affected tissues were identified by comparison to normal tissues. This work has been approved by the Research Ethics Committee of Botucatu School of Medicine, UNESP.
RESULTS AND DISCUSSION
Table 2 shows the main lesions, damaged tissues, and their locations; Figures 1 and 2 show damaged tissue characteristics from MRI of the bite site. Edema was observed in most patients (n=9); it was characterized in the MR images as a thickening of subcutaneous cellular tissue around the bitten limb or restricted to the inner or outer side. Lesion associated with hemorrhage was seen in only one patient; it was frequently associated with edema (n=5). Lesions were seen in perimuscular areas (n=6), subcutaneous (n=5), and muscular tissue (n=4). Hemorrhage, or the presence of blood degradation components, seen at the bite site in the skeletal muscles or subcutaneous tissue is the result of a vascular lesion and local hypervascularization; this is seen as a high signal in T1 (iso or hyper-intense) in MRI (Figure 2). Pathogenesis of local lesions has been specifically studied in relation to skin alterations (1,7,15,18). There are no many reports in literature about the effect of venom on skeletal muscles (5,8-10,18,19). Edema and hemorrhage onset are rapid after venom injection; local edema is a typical sign in Bothrops sp envenoming caused by interstitial liquid accumulation in the tissues (6,10,11,13,16). Our results are in agreement with experimental studies (1,7) using Bothrops jararaca venom; these have reported hemorrhage in skin and muscular tissue followed by necrosis and severe inflammatory reaction (11-14,16). Other studies of severe Bothrops sp envenoming lesions evaluated by computerized tomography imaging showed damage of the deep muscular tissue, increased subcutaneous tissue volume, and alteration in vessel diameters in the areas adjacent to bite site, without indications of hemorrhage and myonecrosis (22). Similar results were obtained in this study. It is important to mention that myonecrosis was not seen in the MR images of the bite site, a widely reported finding in anatomical and histopathological experimental studies (12-14,16,18,19). These observations may suggest that myonecrosis, observed in experimental studies, may be related to the sensitivity of experimental animals, venom dose, and severity of the envenoming. Moreover, no severe case was evaluated in present studies. In this study, MRI allowed the identification and characterization of lesions and the main damaged tissues as they are seen in a clinical study of Bothrops sp envenoming. Edema and hemorrhage were seen in part of or the complete subcutaneous and muscular tissues and perimuscular areas of the affected limb.
|Table 2. Main lesions and damaged tissues evaluated by MRI in patients bitten by Bothrops snakes.|
RMI obtained post-contrast T1 sequence spin-echo
|Figure 1. Bite site lesion characteristics of Bothrops sp envenoming shown in MRI. The arrows indicate subcutaneous tissue edema (A); muscular tissue edema in the right ankle (B); and hemorrhage in the perimuscular areas of the left calf (C,D).|
N= Normal limb
|Figure 2. Bite site edema and hemorrhage characteristics of Bothrops sp envenoming in muscular tissue shown in MRI. The arrows indicate: edema and hemorrhage with high signal in T1, and enhancement after contrast injection in the right ankle (A,B) and right forearm (C,D). Note extensive hemorrhage represented by a band of high signal.|
The author wishes to thank CAPES (Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and the staff of the Tropical Diseases Unit, Botucatu School of Medicine, UNESP.
1 AMORIM MF., MELLO RF., SALIBA F. Envenenamento botrópico e crotálico. Contribuição para o estudo experimental comparado das lesões. Mem. Inst. Butantan, 1951, 23, 63-108. [ Links ]
2 BARRAVIERA B. Acute-phase response in snakebite. Rev. Inst. Med. Trop. São Paulo, 1994, 36, 479. [ Links ]
3 BARRAVIERA B. Ofídios: estudo clínico dos acidentes. Educação médica continuada em infectologia. Rio de Janeiro: EPUB, 1999. 46p. [ Links ]
4 BARRAVIERA B., LOMONTE B., TARKOWSKI A., HANSON LA; MEIRA DA. Acute-phase reactions, including cytokines, in patients bitten by Bothrops and Crotalus snakes in Brasil. J. Venom. Anim. Toxins, 1995, 1, 11-22.
5 BRENES F., GUTIÉRREZ JM., LOMONTE B. Immunohisthochemical demonstration of the binding of Bothrops asper myotoxin to skeletal muscle sarcolemma. Toxicon, 1987, 25, 574-7. [ Links ]
6 CURY Y., TEIXEIRA CFP., SUDO LS. Edematogenic responses induced by Bothrops jararaca venom in rats: role of lymphocytes. Toxicon, 1994, 32, 1425-31. [ Links ]
7 EICHBAUM FW. Ação dermatotóxica de venenos ofídicos e sua neutralização pelos antivenenos. Mem. Inst. Butantan, 1947, 20, 79-94. [ Links ]
8 FONSECA MG. Tissue lesions in patients bitten by Bothrops and Crotalus snakes: clinical, laboratory, and magnetic resonance evaluations. J. Venom. Anim. Toxins, 2001, 7, 146-7.
9 FONSECA MG., MATHIAS MRC., YAMASHITA S., MORCELI J., BARRAVIERA B. Efeito dos venenos botrópicos e crotálicos sobre os tecidos humanos avaliados por ressonância magnética nuclear. Rev. Bras. Toxicol., 1999, 12, supl, 80. [ Links ]
10 GABOW PA., KAEHNY WO., KELLEHER SP. The spectrum of rhabdomyolysis. Medicine, 1982, 61, 141-52. [ Links ]
11 GUTIÉRREZ JM. Local pathological effects induced by Bothrops snake venoms. Mem. Inst. Butantan, 1990, 52,supl., 37-8. [ Links ]
12 GUTIÉRREZ JM., CHAVES F. Efectos proteolítico, hemorragico y mionecrotico de los venenos de serpientes costarricenses de los generos Bothrops, Crotalus y Lachesis. Toxicon, 1980, 18, 315-21. [ Links ]
13 GUTIÉRREZ JM., LOMONTE B. Local tissue damage induced by Bothrops snake venoms. A review. Mem. Inst. Butantan, 1989, 51, 211-23. [ Links ]
14 GUTIÉRREZ JM., ARROYO O., BOLAÑOS R. Mionecrosis, hemorragia y edema inducidos por el veneno de Bothrops asper en ratón blanco. Toxicon, 1980, 18, 603-10. [ Links ]
15 JORGE MT., RIBEIRO LA. Infections in the bite site after envenoming by snakes of the Bothrops genus. J. Venom. Anim. Toxins, 1997, 3, 264-72.
16 LOMONTE B. Tissue damage and inflammation induced by snake venoms. Göteborg: University of Goteborg, 1994. (Thesis-Doctorate). [ Links ]
17 PANEPUCCI H., DONOSO JP., TANNÚS A., BECKMAN N., BONAGAMBA T. Novas imagens do corpo. Ciênc. Hoje, 1985, 4, 46-56. [ Links ]
18 QUEIROZ LS., PETTA CA. Histopathological changes caused by venom of urutu snake (Bothrops alternatus) in mouse skeletal muscle. Rev. Inst. Med. Trop. São Paulo, 1984, 26, 247-53. [ Links ]
19 QUEIROZ LS., SANTO NETO H., ASSAKURA MT., REICHEL AP., MANDELBAUM FR. Pathological changes in muscle caused by haemorrhagic and proteolytic factors from Bothrops jararaca snake venom. Toxicon, 1985, 23, 341-5. [ Links ]
20 VARANDA EA., GIANNINI MJSM. Bioquímica dos venenos de serpentes. In: BARRAVIERA B. Aspectos clínicos e terapêuticos dos acidentes por animais peçonhentos. Rio de Janeiro: EPUB, 1999: 205-23. [ Links ]
21 VITAL BRAZIL O. Peçonhas. In: COBERT CE. Farmacodinâmica. Rio de Janeiro: Guanabara Koogan, 1982: 1044-74. [ Links ]
22 ZANARDI VS, BUCARETCHI F., TOURINHO FSV., FONSECA MRCC., DOUGLAS JL., ZAMBRONE FAD., VIEIRA RJ. Avaliação tomografica do segmento anatômico comprometido em quatro acidentes graves por Bothrops. Rev. Bras. Toxicol., 1993, 6, supl., 22. [ Links ]
Received July 13, 2001
Accepted August 28, 2001
M. G. Fonseca - Rua: Bartolomeu Bueno Filho, 405, 15060-230, São José do Rio Preto, São Paulo, Brasil.