University of Alabama at Birmingham

Gorgas Case 2018-04

Universidad Peruana Cayetano Heredia
The following case was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2018 Gorgas Course participants. 
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History: At 8pm, a 68-year-old male was bitten twice, on the index and middle fingers of his right hand, while trying to catch a snake outside his house. At first, there was only mild stabbing pain, but after 1h the hand had become swollen and tender. These symptoms increased, prompting his presentation to the ED 3½h after the bites.

Epidemiology: He was born in Huancayo but had dwelled in Lima since he was 14 years old apart from trips to Tarapoto and Tingo Maria in the Amazon region. He lives in Collique, a hilly (cerro) northern suburb of Lima, 20 k north of UPCH. His house is made of mats and has no cement floor. He works selling Aloe plants in a market.

Physical Examination: BP: 110/70mmHg. HR: 61. RR: 20. T: 36C. Sat 98% at FiO2 21%. The patient felt hot and sweaty. There was tense, tender swelling and erythema of the fingers and right hand extending up to the elbow. He had tender enlarged lymph glands in the right axilla. By the next day, the whole right arm was swollen and he was unable to raise his right arm because of stiffness and pain (Image A). Subsequently, more bruising appeared on the right arm and the right side of his chest (Image B) and his hand and arm felt numb.

Laboratory: Hematocrit:36%. Hemoglobin:12 g/dl. WBC: 10.6 (0% bands, 63.5% segmented, 10.2% eosinophils) Creatinine:0.9mg/dl. Urea:31 mg/dl. INR: 1.19, PT: 14.9, aPTT: 38.5. Whole blood clotting time: 6min. Bleeding time: 3min. Urine Exam: density 1024, pH 5, 2-3leu/field, 2-3 RBC/field, sparse epithelial cells.


UPCH Case Editors: Carlos Seas, Course  Director / Karen Luhmann, Associate Coordinator
UAB Case Editor: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director
Diagnosis: 

Envenoming by desert lancehead pit viper (Bothrops pictus or B. roedingeri)

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Discussion:

Species diagnosis
After being bitten, the patient killed the snake, cut off its head and bit its tail for superstitious reasons. These sorts of rituals are common in regions where snake-bites are common, reflecting people’s almost supernatural dread of venomous snakes. The reason he gave us for trying to catch a dangerous snake was that he wanted to use the skin, as “leather”, to make some kind of art work. He had killed a similar snake only one week previously. His family was asked to bring in the remains of the snake to allow a species diagnosis, but, initially, only the headless skinned body was provided, which was impossible to identify! Finally, they were persuaded to bring the flayed skin, whose dark blotched and zig-zagged dorsal pattern and rough scales were diagnostic of the desert lance-headed pit vipers (Bothrops pictus and B. roedingeri) (“jergón de la costa”, or “víbora”) (Image C), the only venomous species found in the Lima area. [Campbell, JA, Lamar, WW. (eds.) The Venomomous Reptiles of the Western Hemisphere. Ithaca, Comstock Cornell University, 2nd Ed 2004]. The snake must have exceeded 49 cm in total length, the combined lengths of the body fragments without head and tail tip. Bothrops pictus and B. roedingeri are endemic Peruvian species (Image D & E) found on the western slopes of the Andes, and throughout the coastal foothills and mountains at altitudes between sea level and 2,300 m, from Ancash south to Arequipa. They also occur in some of the drier inland valleys and mountains, such as Chillon and Canta, and cerros in the Cono Norte of metropolitan Lima. These two species are superficially similar in appearance, have been widely confused and, indeed are, according to some authorities, the same species (http://reptile-database.reptarium.cz/species?genus=Bothrops&species=pictus). Bothrops roedingeri differs from B. pictus in being longer and more slender (up to 100cm in total length compared to 60cm), having fewer dorsal scale rows and more ventral scales, and inhabiting lower altitudes closer to the coast as far North as La Libertad [Campbell, JA, Lamar, WW. (eds.) The Venomomous Reptiles of the Western Hemisphere. Ithaca, Comstock Cornell University, 2nd Ed 2004]. 

Evolution of envenoming
After receiving two bites on fingers of his right hand, our patient developed, over the next few days, progressive pain, dysfunction, swelling and bruising of the entire arm, axilla and right side of his trunk (Image B) which had largely resolved by the time he was discharged 12 days later. He had no symptoms of systemic envenoming. It is interesting that his extensive local bruising occurred, despite the lack of coagulopathy or thrombocytopenia, implying direct damage to the endothelium of adjacent blood vessels by large molecular weight snake venom haemorrhagins that had spread through the lymphatic system from the site of the bite [Toxins (Basel). 2016;8(4):93]. Literature reports and local snake-bite experts in the Lima area have not distinguished bites by B. pictus from those by B. roedingeri. A study of 23 patients with presumed B. pictus bites admitted to Cayetano Hospital in 1990-1998 described local swelling, erythema, bruising (sometimes extensive), and blistering as the commonest features [Folia Dermatol Perú 1998;.9: 41-48]. Coagulopathy was detected in 6 of 8 cases and one developed acute kidney injury. 75% were treated with INS antivenom and there were no fatalities. However, our patient had heard of a recent snake-bite fatality in Puente Piedro, also in the Cono Norte of Lima.

Envenoming is not inevitable after a bite by a venomous snake even when fang puncture marks are evident on the skin. The phenomenon of “dry bite” has been well documented in about 50-80% of snake-bite victims [Toxicon 2017;133:63-67]. It was well illustrated by a patient seen in the ED of Cayetano Hospital only 12 days after our patient was admitted. Despite fang marks and the evidence of a dead desert lancehead, he developed no symptoms or signs of envenoming.

Mechanism of haemorrhage
The venom of B. pictus contains an array of toxic proteins and peptides typical of Viperidae, but compared to some other Peruvian pit vipers, such as the notorious B. atrox of the Amazon region (see case 2, 2014), it has a higher proportion of haemorrhagins [J Proteomics 2012;75(7):2181-95]. These are large molecular weight P-III snake venom metalloproteinases (SVMPs) that possess an N-terminal Zn2+ - dependent catalytic domain, disintegrin-like domain and C-terminal cysteine-rich region. They degrade matrix proteins in the capillary basement membrane, resulting in spontaneous systemic haemorrhage, a dangerous effect of envenoming [Toxins (Basel) 2016;8(4):93]. A variety of venom toxins, including SVMPs, and an L-amino acid oxidase from B. pictus venom, can inhibit platelet agglutination [Toxicon 2017;139:74-86]. Although our patient did not develop thrombocytopenia, his platelet function may have been impaired, contributing to the extent of local bleeding.

Access to antivenom treatment
Our patient was initially frustrated in his search for appropriate treatment. First, he went to the local hospital, but, after 2h, was sent away because no antivenom could be found. He then visited another hospital 11k away, but it also lacked this essential drug. Finally, at UPCH, he was given antivenom because of the extent and progression of the local swelling, even though there was no evidence of systemic envenoming. One vial of Peruvian Instituto Nacional de Salud (INS) suero antibotrópico polivalente was administered 13 h after the bite, and a second vial 3 h later, without any adverse reactions. He felt relief of pain 3h after the second dose. This antivenom is raised in horses by hyperimmunising them with venoms of desert lancehead (Bothrops pictus), common lancehead (B. atrox), Brazil’s lancehead (B. brazili), Barnett’s lancehead (B. barnetti) and hognosed lancehead (Bothrocophias hyoprora) and extracting whole IgG from the resulting plasma by ammonium sulfate fractionation [Toxicon 2016;122:67-77]. Preserved specimens of four of these species, loaned by INS, were studied by the Gorgas participants during a pioneering snake identification workshop (Image F).

We would like to thank Professor David Warrell, Emeritus Professor, Oxford University,  for providing insightful case discussion.