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Toxicon 54 (2009) 354360

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Toxicon
journal homepage: www.elsevier.com/locate/toxicon

Local envenoming by the Western hognose snake (Heterodon nasicus): A


case report and review of medically signicant Heterodon bites
Scott A. Weinstein a, b, *, Daniel E. Keyler c, d,1
a
Department of Clinical Toxinology, Womens and Childrens Hospital, 71 King William Street, North Terrace, Adelaide, South Australia 5000, Australia
b
Royal Adelaide Hospital, Internal Medicine Service, Clinic 275, 275 North Terrace, Adelaide, South Australia 5000, Australia
c
Hennepin County Medical Center, Department of Medicine, Division of Clinical Pharmacology, 701 Park Avenue, G5, Minneapolis, MN 55415-1829, USA
d
Department of Experimental & Clinical Pharmacology, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455, USA

a r t i c l e i n f o a b s t r a c t

Article history: A case of clinically signicant local envenoming resulting from a bite inicted by a Western
Received 29 December 2008 hognose snake, Heterodon nasicus, is described. The patient was bitten while offering
Received in revised form 13 April 2009 a juvenile mouse to a captive snake. The snake maintained a grip on the patients arm (left
Accepted 14 April 2009
anticubital fossa) for several minutes. The bite resulted in marked edema, ecchymoses,
Available online 23 April 2009
lymphadenopathy, cutaneous signs suggestive of mild cellulitis and blister formation.
There were no systemic effects. Recovery was complete after approximately ve months.
Keywords:
Several documented Heterodon sp. bites with signicant clinical effects are reviewed. This
Hognose snake
Heterodon common xenodontine colubrid must be considered capable of inicting medically signif-
Envenoming icant bites. It is currently unclear whether the pathological changes associated with these
Type I hypersensitivity bites are due to specic Duvernoys secretion components, Type I hypersensitivity or
Duvernoys secretion a combination of these. The inuence of the feeding response on the severity of clinical
effects is considered as is the discrepancy between experimentally veried pharmaco-
logical activities of Duvernoys secretions from Heterodon sp. and medical sequelae of
documented bites. Although hognose snakes may uncommonly produce medically
signicant bites, they should not be considered dangerous or venomous. Captive speci-
mens should be handled carefully, particularly when offered food.
2009 Elsevier Ltd. All rights reserved.

1. Introduction the largest discrete and polyphyletic group of caeno-


phidians, referred to as the family Colubridae for conve-
Most extant snakes belong to the superfamily, Caeno- nience, is veried only for a handful of the approximately
phidia (Colubroidea), including all of the medically 20002500 taxa in this diversied and taxonomically arti-
important venomous snakes such as elapids, viperids and cial assemblage (Minton, 1990; Weinstein and Kardong,
atractaspids. Clinically important cases of envenoming by 1994; Warrell, 2004; Weinstein et al., in press). An unde-
snakes are most often caused by bites from elapid and termined percentage of colubrid snakes secrete toxins from
viperid snakes (Minton, 1974; Russell, 1983; Meier and a low-pressure (due to little or no direct muscle attachment
White, 1995; Chippaux, 1998). The medical importance of on the gland) secretory system (Duvernoys gland) that may
or may not be associated with posterior enlarged maxillary
teeth that may be grooved (McKinstry, 1983; Weinstein and
* Corresponding author at: Royal Adelaide Hospital, Internal Medicine Kardong, 1994; Kardong, 1996; Mackessy, 2002). Fatal
Service, Clinic 275, 275 North Terrace, Adelaide, South Australia 5000,
envenomations or serious morbidity inicted by the African
Australia. Tel.: 61 08 8 222 5075; fax: 61 08 8 232 3504.
E-mail addresses: venfraction@yahoo.com, herptoxmed@msn.com
dispholidines, Dispholidus typus, Thelotornis kirtlandii and
(S.A. Weinstein), keyle001@umn.edu (D.E. Keyler). Thelotornis capensis and the Asian natricines, Rhabdophis
1
Tel.: 1 612 873 4051. subminiatus and Rhabdophis tigrinus have been thoroughly

0041-0101/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.toxicon.2009.04.015
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354360 355

documented (Minton, 1990; Weinstein and Kardong, 1994; specimens), in particular from H. nasicus, that consisted of
Mackessy, 2002). Accumulating data suggests that Philo- edema of varying severity, uncomplicated lacerations and
dryas sp. probably are medically important in South local pain (Bragg, 1960; Grogan, 1974; Phillips et al., 1997).
America (Nickerson and Henderson, 1976; Kuch and Jes- Hornfeldt and Keyler (1987) assessed the toxicity of
berger, 1993; Nishioka and Silveira, 1994; Fowler and Sal- Heterodon sp. and reviewed accounts of several clinically
omao, 1994; Warrell, 2004). The clinical relevance of other signicant Heterodon bites.
colubrid taxa (e.g. Malpolon monspessulanus) (Gonzales, We report here a case of H. nasicus bite that resulted in
1979; Pommier and de Haro, 2007), Boiga irregularis (Fritts signicant local effects. In addition, this case is considered
et al., 1994; Fritts and McCoid, 1999) is supported by limited with several reviewed cases of Heterodon sp. bites that
evidence. Aside from this small sampling of colubrids with resulted in signicant clinical sequelae.
proven capacities to produce human mortality and
morbidity, few documented, evidence-based cases support 2. Case report
the medical importance of other colubrid species (Warrell,
2004; Weinstein et al., in press). A 21-year-old female presented to an emergency
The hognose snakes (Heterodon sp.) and their allies department approximately 34 h after sustaining a bite on
(Lystrophis sp.) have been traditionally considered, and are the left anticubital fossa from a captive young adult
still widely viewed as, members of the colubrid subfamily, (approximately 45 cm, total length) Western hognose
xenodontinae. It is noteworthy that a recent taxonomic snake, H. nasicus. The patient had no prior history of Het-
study recommended re-assignment of Heterodon sp. and erodon bites. The snake was a long-term captive in
Lystrophis sp. to the subfamilies, heterodontinae and xen- a university biology department collection, and she was
odontinae, respectively, of the family, Dipsadidae (Vidal bitten while feeding the snake a small mouse. She reported
et al., 2007). Traditionally, the xenodontines are a diverse that the snake maintained a grip on the arm for approxi-
group that consists of at least 90 genera and greater than mately 35 min and had to be removed by manual force
500 species (Vidal et al., 2000; Dowling et al., 1996). Several (the jaws were pried open by forcible lifting of the maxilla
xenodontines (e.g. Philodryas sp.) have been implicated in via the snout). The resulting punctures bled freely for
clinically signicant envenomings (for a review, see War- several minutes following the bite. During the rst 3 h
rell, 2004). The North American genus, Heterodon, consists following the bite, she experienced no appreciable pain or
of four species (H. nasicus, Heterodon platirhinos, Heterodon swelling. She later reported that the swelling noticeably
simus and Heterodon kennerlyi; Smith et al., 2003) and increased several hours after the bite, and thus sought local
several subspecies. The Western hognose snake, H. nasicus medical attention. Tetanus immune status was conrmed
is a small to medium-sized (average adult size approxi- and 1.0 g of ceftriaxone, i.v. was administered. Edema of the
mately 50 cm total length) species (Fig. 1). It is found in left arm increased and expanded and, due to concerns of
sandy/loose soil biotopes in prairie, rocky environments medical personnel unfamiliar with snakebites, the patient
and coastal habitats. It ranges from southern Canada to was transferred to a Level I trauma center. Upon arrival,
northern Mexico with a distribution bordered in the east by toxicology consultation was obtained. Approximately 5 h
Illinois and by Colorado and Wyoming in the west (Smith after the incident, noted was edema involving the left
and Brodie, 1982; Wright and Wright, 1994). Hognose elbow extending to the wrist, mild ecchymosis and two
snakes are popular pets and are regularly available from clearly dened punctures proximal to the anticubital fossa.
animal dealers and private reptile breeders. The patients laboratory results (including complete blood
The envenoming potential of Heterodon sp. has been prole, comprehensive metabolic prole and basic coagu-
debated since the mid-twentieth century. Several authors lation tests) all were within normal limits on presentation.
have reported local effects from bites by these snakes She complained of mild pain associated with the increased
(usually accidental bites inicted during feedings of captive tension of the edema. Following admission, she remained
stable and all laboratory tests remained unremarkable. On
examination 24 h after the bite, the patients left arm
exhibited marked edema and lymphadenopathy (Fig. 2,
upper panel). At 48 h, blister formation both distal and
proximal to the bite involving the left anticubital fossa and
lateralventral wrist was observed (Fig. 2, lower panel). The
patient was discharged with a prescribed regimen of
diphenhydramine. Shortly after discharge (approximately
30 h after the bite), she followed-up with her primary care
physician and aspirate was obtained from several blisters
and sent for culture/sensitivity. This aspirate remained
culture negative. The patient received local wound care,
amoxicillin/clavulanate (875 mg, p.o., twice per day) was
prescribed and desloratidine was substituted for the
diphenhydramine. Acetominophen/hydrocodone (500/
5 mg) as needed was prescribed due to left arm pain
Fig. 1. A young adult specimen of the Western hognose snake, Heterodon encountered during positioning for sleep. She also noted
nasicus (photo courtesy of A.B. Sheldon). stiffness in her left wrist and digits. The blisters drained
356 S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354360

Fig. 2. Upper panel: Left arm, 24 h post-envenoming. Note the edema. Lower panel: Left arm, 48 h post-envenoming. Note the blister formation at the lateral-
ventral wrist. Bite site indicated by arrow.

quantities of serous discharge that required regular days after the incident, the patient reported pruritis of the
multiple changes of wound dressings. Review at 72 h post- left forearm with reduced ecchymoses and resolving blis-
bite showed reduced edema, ecchymosis and an increased ters. The edema, pruritis and stiffness improved during the
zone of erythema suggestive of cellulitis (Fig. 3, upper following two weeks. At ten weeks post-envenoming,
panel). At 96 h post-envenoming, noted were persistent multiple milia were observed at the wound site, most
edema of the left hand, ecchymosis and blistering of the notably at the wound margin. Healing was complete at ve
medial-ventral left arm (Fig. 3, lower panel). Twenty-eight months.
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354360 357

Fig. 3. Upper panel: Left arm, 72 h post-envenoming. Edema at bite site is reduced. Lower panel: Left arm, 96 h post-bite. Note the blisters and ecchymoses. The
left hand exhibits persistent edema (right lower panel).

3. Discussion effects. Hill and Mackessy (2000) reported that H. nasicus


Duvernoys secretions exhibited low phosphodiesterase,
3.1. The etiology of medically signicant Heterodon bites: moderatehigh protease activity and lacked PLA2. The
Duvernoys secretions, hypersensitivity and other possible saliva of the subspecies, H. n. nasicus, contained high levels
contributing factors of PLA2 and no proteolytic activity (Hill and Mackessy,
2000). A mean liquid venom yield from two specimens of
Clinical manifestations observed in this patient were H. n. nasicus (total length, 48 cm) and H. n. kennerlyi (total
similar to those noted in some mild local crotaline enve- length, 32 cm) was 24 mL and 15 mL, respectively (Hill and
nomations. The patient exhibited moderate edema, ecchy- Mackessy, 2000). The Heterodon oral secretions studied did
moses, blister formation and, possibly, mild cellulitis. These not contain any detectable thrombin-like, hyaluronidase or
pathologic changes were possibly caused by the combined kallikrein-like activities (Hill and Mackessy, 2000).
activities of several Duvernoys secretion components and Pharmacological study of Duvernoys secretion from
Type I hypersensitivity. To date, there are few data H. platirhinos demonstrated induction of neuromuscular
regarding the components from oral secretions of Hetero- blockade in the dissected frog sciatic nervegastrocnemius
don sp. that might be responsible for the observed clinical preparation and antagonism of acetylcholine and histamine
358 S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354360

responses of isolated rat duodenum (Young, 1992). The likelihood of introduction of a larger volume of Duvernoys
author suggested a possible mode of action resembling that secretion into the wound and may result in a clinically
of acetylcholinesterase. With the ongoing identication of signicant bite. Rapid (i.e. quick release) bites with subse-
post-synaptic neurotoxins (three-nger neurotoxins, quent envenoming by rear-fanged snakes certainly occur
previously referred to as various types of long-chain and (Warrell, 2004). However, available well-documented cases
short-chain neurotoxins) in Duvernoys secretions suggest that these are less common than those caused by
(Levinson et al., 1976; Weinstein and Kardong, 1994; a protracted bite.
Broaders et al., 1999; Fry et al., 2003; Lumsden et al., 2005;
Pawlak et al., 2006), it is possible that such toxins occur in 3.3. Conclusions, additional considerations and some
Heterodon sp. and were detected in the study conducted by recommendations for management of medically signicant
Young (1992). Available data, including clinical observations Heterodon bites
from the present case, suggest that post-synaptically active
toxins detected in vitro play no medically relevant role in In summary, we have described a bite inicted by a H.
Heterodon bites. Similar to the majority of well-documented nasicus that resulted in signicant local morbidity. Hognose
medically signicant colubrid bites, the primary clinical snakes are phlegmatic and mild captives and cases such as
manifestations are edema, bleeding, ecchymoses and described here are rare. Therefore, these snakes should not
blister/bleb formation. To date, there is no evidence doc- be viewed as venomous or dangerous, nor subjected to
umenting or supporting any systemic effects of a Heterodon regulation. It is advisable that captive specimens be
bite. The discrepancy between the in vitro data and clinical handled with care (especially when offered food) and any
manifestations may be due to taxa (anuran)-specic medically signicant bites be promptly reviewed by
neurotoxins in the secretion as well as mammalian a qualied health professional. Similarly, a provisional
responses to other components such as proteolytic hemor- caution is warranted in regard to the South American
rhagins, myotoxins, etc. The occurrence of prey-specic hognose snakes (Lystrophis sp). Although there are anec-
toxins in Duvernoys secretion from Heterodon sp. has been dotal reports regarding mild local effects resulting from
considered by several researchers (e.g. Minton and Minton, bites inicted by Lystrophis sp. (Warrell, 2004), there are no
1980; Young, 1992). Recently, avian and/or saurian-specic data regarding specic toxicity of oral secretions from these
toxins have been characterized from the Duvernoys secre- snakes. Kardong (personal communication) has dissected
tions of the mangrove snake, Boiga dendrophila (Pawlak Duvernoys glands from Lystrophis sp. It is likely that all
et al., 2006) and brown tree snake, B. irregularis (Pawlak members of the genus have Duvernoys glands and produce
et al., 2009). secretion of unknown potency. Many Lystrophis sp. are
Type I hypersensitivity to snake venoms is a recognized attractively tri-colored and are reasonably popular in
consequence of sensitization by previous envenomings, private collections.
frequent handling of venomous snakes, and repetitive Although there is no specic treatment (other than
exposure to crude or lyophilized venoms (Reimers et al., wound care and symptomatic management) recom-
2000; Medeiros et al., 2007; Malina et al., 2008). Individual mended for medically signicant bites inicted by Hetero-
history of atopy probably is a contributing factor (Medeiros don sp., we recommend that patients bitten by these and
et al., 2007). The potential development of hypersensitivity other colubrids of unknown medical importance be
to antigens shared among colubrid (or, possibly, among observed in a medical facility as long as necessary to rule
many ophidian species) oral secretions may play an out development of any signicant local or systemic effects
important contributing role in medically signicant bites following a bite. Comprehensive laboratory testing
from Heterodon sp. and other colubrids. Assessment of (including differential blood count, coagulation panel,
serum IgE levels and clinical responsiveness to corticoste- creatine kinase and comprehensive metabolic panel)
roid regimens during such episodes may clarify the etiology should be performed along with meticulous wound care.
of these symptoms. The medical team should remain aware of the possibility of
Type I hypersensitivity in patients bitten by any ophidian
3.2. Features of previously reported cases: does the feeding species including Heterodon. Assessment of this risk should
response inuence the severity of medically signicant be performed by procurement of a careful history regarding
Heterodon bites? handling of snakes, cleaning cages of captive specimens,
handling shed skins and documentation of previous bites
The present case is congruous with previously docu- by venomous and non-venomous species.
mented reports suggesting that some bites from H. nasicus Referral should be considered as required, and close
may result in medically signicant sequelae (Hornfeldt and follow-up is essential. Use of prophylactic antibiotics in
Keyler, 1987). Edema, ecchymoses and, occasionally, most snakebites is not supported by available evidence
persistent discharge from tooth punctures are sequelae (LoVecchio et al., 2002; White and Dart, 2008), however, in
common in most reports of medically signicant Heterodon the case of secondary infection, a broad spectrum antibiotic
bites. Table 1 summarizes previously reported cases of with b-lactamase inhibitor (e.g. amoxicillin/clavulanate,
Heterodon bites. 875 mg/125 mg, twice per day for 7 days) may be
As suggested from the history of some cases of Hetero- prescribed. Penicillin allergic patients may be treated with
don sp. bites, elicitation of a feeding response may result in doxycycline, 100 mg, twice per day for 10 days or clinda-
a sustained grip and, possibly, a greater engagement of the mycin, 150400 mg (dose dependent on severity of the
posterior maxillary teeth. This probably increases the infection), four times per day for 7 days. Due to the risk of
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354360 359

Table 1
Previously reported cases of Heterodon bites.

Species Size of offending Age of Reported symptoms/signsa Review by health Time to resolution Reference
specimen (cm) victim (years) professional? of symptoms
Heterodon nasicus 53 NR E, T, BL, burning No Approx. 2 weeks Bragg (1960)
Heterodon platirhinosb 89 16 P (burning), E, N, BL, No 4 months Grogan (1974)
persistent ER, WD
H. nasicus 31 11 E, P, EC Yes 5 days Phillips et al. (1997)
H. nasicus 52 NR P, E, B, PR, BL, WD No 2 days Morris (1985)
H. nasicus NR Middle-aged E, P, EC Yes 3 months Walley (2002)
a
Abbreviations: E-edema; T-tenderness; P-pain; N-nausea; ER-erythema; WD-wound discharge; EC-ecchymoses; B-blistering; BL-bleeding; PR-pruritis;
NR-not reported.
b
In this case the snake did not specically bite the victim. Rather, several teeth were imbedded in the skin while the specimen was feigning death with
mouth agape.

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