Local envenoming by the Western hognose snake (Heterodon nasicus): A case report and review of medically significant Heterodon bites

Abstract

A case of clinically significant local envenoming resulting from a bite inflicted by a Western hognose snake, Heterodon nasicus, is described. The patient was bitten while offering a juvenile mouse to a captive snake. The snake maintained a grip on the patient's arm (left anticubital fossa) for several minutes. The bite resulted in marked edema, ecchymoses, lymphadenopathy, cutaneous signs suggestive of mild cellulitis and blister formation. There were no systemic effects. Recovery was complete after approximately five months. Several documented Heterodon sp. bites with significant clinical effects are reviewed. This common xenodontine colubrid must be considered capable of inflicting medically significant bites. It is currently unclear whether the pathological changes associated with these bites are due to specific Duvernoy's secretion components, Type I hypersensitivity or a combination of these. The influence of the feeding response on the severity of clinical effects is considered as is the discrepancy between experimentally verified pharmacological activities of Duvernoy's secretions from Heterodon sp. and medical sequelae of documented bites. Although hognose snakes may uncommonly produce medically significant bites, they should not be considered dangerous or venomous. Captive specimens should be handled carefully, particularly when offered food.

Full text

Local envenoming by the Western hognose snake (Heterodon nasicus): A
case report and review of medically significant Heterodon bites
Scott A. Weinstein
a
,
b
,
*
, Daniel E. Keyler
c
,
d
,
1
a
Department of Clinical Toxinology, Women’s and Children’s 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
article info
Article history:
Received 29 December 2008
Received in revised form 13 April 2009
Accepted 14 April 2009
Available online 23 April 2009
Keywords:
Hognose snake
Heterodon
Envenoming
Type I hypersensitivity
Duvernoy’s secretion
abstract
A case of clinically significant local envenoming resulting from a bite inflicted by a Western
hognose snake, Heterodon nasicus, is described. The patient was bitten while offering
a juvenile mouse to a captive snake. The snake maintained a grip on the patient’s arm (left
anticubital fossa) for several minutes. The bite resulted in marked edema, ecchymoses,
lymphadenopathy, cutaneous signs suggestive of mild cellulitis and blister formation.
There were no systemic effects. Recovery was complete after approximately five months.
Several documented Heterodon sp. bites with significant clinical effects are reviewed. This
common xenodontine colubrid must be considered capable of inflicting medically signif-
icant bites. It is currently unclear whether the pathological changes associated with these
bites are due to specific Duvernoy’s secretion components, Type I hypersensitivity or
a combination of these. The influence of the feeding response on the severity of clinical
effects is considered as is the discrepancy between experimentally verified pharmaco-
logical activities of Duvernoy’s secretions from Heterodon sp. and medical sequelae of
documented bites. Although hognose snakes may uncommonly produce medically
significant bites, they should not be considered dangerous or venomous. Captive speci-
mens should be handled carefully, particularly when offered food.
Ó2009 Elsevier Ltd. All rights reserved.
1. Introduction
Most extant snakes belong to the superfamily, Caeno-
phidia (¼Colubroidea), including all of the medically
important venomous snakes such as elapids, viperids and
atractaspids. Clinically important cases of envenoming by
snakes are most often caused by bites from elapid and
viperid snakes (Minton, 1974; Russell, 1983; Meier and
White, 1995; Chippaux, 1998). The medical importance of
the largest discrete and polyphyletic group of caeno-
phidians, referred to as the family Colubridae for conve-
nience, is verified only for a handful of the approximately
2000–2500 taxa in this diversified and taxonomically arti-
ficial assemblage (Minton, 1990; Weinstein and Kardong,
1994; Warrell, 2004; Weinstein et al., in press). An unde-
termined percentage of colubrid snakes secrete toxins from
a low-pressure (due to little or no direct muscle attachment
on the gland) secretory system (Duvernoy’s gland) that may
or may not be associated with posterior enlarged maxillary
teeth that may be grooved (McKinstry,1983; Weinstein and
Kardong, 1994; Kardong, 1996; Mackessy, 2002). Fatal
envenomations or serious morbidity inflicted by the African
dispholidines, Dispholidus typus,Thelotornis kirtlandii and
Thelotornis capensis and the Asian natricines, Rhabdophis
subminiatus and Rhabdophis tigrinus have been thoroughly
*Corresponding author at: Royal Adelaide Hospital, Internal Medicine
Service, Clinic 275, 275 North Terrace, Adelaide, South Australia 5000,
Australia. Tel.: þ61 08 8 222 5075; fax: þ61 08 8 232 3504.
E-mail addresses: venfraction@yahoo.com,herptoxmed@msn.com
(S.A. Weinstein), keyle001@umn.edu (D.E. Keyler).
1
Tel.: þ1 612 873 4051.
Contents lists available at ScienceDirect
Toxicon
journal homepage: www.elsevier.com/locate/toxicon
0041-0101/$ – see front matter Ó2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.toxicon.2009.04.015
Toxicon 54 (2009) 354–360

documented (Minton, 1990; Weinstein and Kardong, 1994;
Mackessy, 2002). Accumulating data suggests that Philo-
dryas sp. probably are medically important in South
America (Nickerson and Henderson, 1976; Kuch and Jes-
berger, 1993; Nishioka and Silveira, 1994; Fowler and Sal-
oma
˜o, 1994; Warrell, 2004). The clinical relevance of other
colubrid taxa (e.g. Malpolon monspessulanus)(Gonzales,
1979; Pommier and de Haro, 2007), Boiga irregularis (Fritts
et al., 1994; Fritts and McCoid,1999) is supported by limited
evidence. Aside from this small sampling of colubrids with
proven capacities to produce human mortality and
morbidity, few documented, evidence-based cases support
the medical importance of other colubrid species (Warrell,
2004; Weinstein et al., in press).
The hognose snakes (Heterodon sp.) and their allies
(Lystrophis sp.) have been traditionally considered, and are
still widely viewed as, members of the colubrid subfamily,
xenodontinae. It is noteworthy that a recent taxonomic
study recommended re-assignment of Heterodon sp. and
Lystrophis sp. to the subfamilies, heterodontinae and xen-
odontinae, respectively, of the family, Dipsadidae (Vidal
et al., 2007). Traditionally, the xenodontines are a diverse
group that consists of at least 90 genera and greater than
500 species (Vidal et al., 2000; Dowling et al., 1996). Several
xenodontines (e.g. Philodryas sp.) have been implicated in
clinically significant envenomings (for a review, see War-
rell, 2004). The North American genus, Heterodon, consists
of four species (H. nasicus,Heterodon platirhinos,Heterodon
simus and Heterodon kennerlyi;Smith et al., 2003) and
several subspecies. The Western hognose snake, H. nasicus
is a small to medium-sized (average adult size approxi-
mately 50 cm total length) species (Fig. 1). It is found in
sandy/loose soil biotopes in prairie, rocky environments
and coastal habitats. It ranges from southern Canada to
northern Mexico with a distribution bordered in the east by
Illinois and by Colorado and Wyoming in the west (Smith
and Brodie, 1982; Wright and Wright, 1994). Hognose
snakes are popular pets and are regularly available from
animal dealers and private reptile breeders.
The envenoming potential of Heterodon sp. has been
debated since the mid-twentieth century. Several authors
have reported local effects from bites by these snakes
(usually accidental bites inflicted during feedings of captive
specimens), in particular from H. nasicus, that consisted of
edema of varying severity, uncomplicated lacerations and
local pain (Bragg, 1960; Grogan, 1974; Phillips et al., 1997).
Hornfeldt and Keyler (1987) assessed the toxicity of
Heterodon sp. and reviewed accounts of several clinically
significant Heterodon bites.
We report here a case of H. nasicus bite that resulted in
significant local effects. In addition, this case is considered
with several reviewed cases of Heterodon sp. bites that
resulted in significant clinical sequelae.
2. Case report
A 21-year-old female presented to an emergency
department approximately 3–4 h after sustaining a bite on
the left anticubital fossa from a captive young adult
(approximately 45 cm, total length) Western hognose
snake, H. nasicus. The patient had no prior history of Het-
erodon bites. The snake was a long-term captive in
a university biology department collection, and she was
bitten while feeding the snake a small mouse. She reported
that the snake maintained a grip on the arm for approxi-
mately 3–5 min and had to be removed by manual force
(the jaws were pried open by forcible lifting of the maxilla
via the snout). The resulting punctures bled freely for
several minutes following the bite. During the first 3 h
following the bite, she experienced no appreciable pain or
swelling. She later reported that the swelling noticeably
increased several hours after the bite, and thus sought local
medical attention. Tetanus immune status was confirmed
and 1.0 g of ceftriaxone, i.v. was administered. Edema of the
left arm increased and expanded and, due to concerns of
medical personnel unfamiliar with snakebites, the patient
was transferred to a Level I trauma center. Upon arrival,
toxicology consultation was obtained. Approximately 5 h
after the incident, noted was edema involving the left
elbow extending to the wrist, mild ecchymosis and two
clearly defined punctures proximal to the anticubital fossa.
The patient’s laboratory results (including complete blood
profile, comprehensive metabolic profile and basic coagu-
lation tests) all were within normal limits on presentation.
She complained of mild pain associated with the increased
tension of the edema. Following admission, she remained
stable and all laboratory tests remained unremarkable. On
examination 24 h after the bite, the patient’s 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
lateral–ventral 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
encountered during positioning for sleep. She also noted
stiffness in her left wrist and digits. The blisters drained
Fig. 1. A young adult specimen of the Western hognose snake, Heterodon
nasicus (photo courtesy of A.B. Sheldon).
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354–360 355

quantities of serous discharge that required regular
multiple changes of wound dressings. Review at 72 h post-
bite showed reduced edema, ecchymosis and an increased
zone of erythema suggestive of cellulitis (Fig. 3, upper
panel). At 96 h post-envenoming, noted were persistent
edema of the left hand, ecchymosis and blistering of the
medial-ventral left arm (Fig. 3, lower panel). Twenty-eight
days after the incident, the patient reported pruritis of the
left forearm with reduced ecchymoses and resolving blis-
ters. The edema, pruritis and stiffness improved during the
following two weeks. At ten weeks post-envenoming,
multiple milia were observed at the wound site, most
notably at the wound margin. Healing was complete at five
months.
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.
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354–360356

3. Discussion
3.1. The etiology of medically significant Heterodon bites:
Duvernoy’s secretions, hypersensitivity and other possible
contributing factors
Clinical manifestations observed in this patient were
similar to those noted in some mild local crotaline enve-
nomations. The patient exhibited moderate edema, ecchy-
moses, blister formation and, possibly, mild cellulitis. These
pathologic changes were possibly caused by the combined
activities of several Duvernoy’s secretion components and
Type I hypersensitivity. To date, there are few data
regarding the components from oral secretions of Hetero-
don sp. that might be responsible for the observed clinical
effects. Hill and Mackessy (2000) reported that H. nasicus
Duvernoy’s secretions exhibited low phosphodiesterase,
moderate–high protease activity and lacked PLA
2
. The
saliva of the subspecies, H. n. nasicus, contained high levels
of PLA
2
and no proteolytic activity (Hill and Mackessy,
2000). A mean liquid ‘‘venom’’ yield from two specimens of
H. n. nasicus (total length, 48 cm) and H. n. kennerlyi (total
length, 32 cm) was 24
m
L and 15
m
L, respectively (Hill and
Mackessy, 2000). The Heterodon oral secretions studied did
not contain any detectable thrombin-like, hyaluronidase or
kallikrein-like activities (Hill and Mackessy, 2000).
Pharmacological study of Duvernoy’s secretion from
H. platirhinos demonstrated induction of neuromuscular
blockade in the dissected frog sciatic nerve–gastrocnemius
preparation and antagonism of acetylcholine and histamine
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).
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354–360 357

responses of isolated rat duodenum (Young, 1992). The
author suggested a possible mode of action resembling that
of acetylcholinesterase. With the ongoing identification of
post-synaptic neurotoxins (‘‘three-finger neurotoxins’’,
previously referred to as various types of long-chain and
short-chain neurotoxins) in Duvernoy’s secretions
(Levinson et al., 1976; Weinstein and Kardong, 1994;
Broaders et al., 1999; Fry et al., 2003; Lumsden et al., 2005;
Pawlak et al., 2006), it is possible that such toxins occur in
Heterodon sp. and were detected in the study conducted by
Young (1992). Available data, including clinical observations
from the present case, suggest that post-synaptically active
toxins detected in vitro play no medically relevant role in
Heterodon bites. Similar to the majority of well-documented
medically significant colubrid bites, the primary clinical
manifestations are edema, bleeding, ecchymoses and
blister/bleb formation. To date, there is no evidence doc-
umenting or supporting any systemic effects of a Heterodon
bite. The discrepancy between the in vitro data and clinical
manifestations may be due to taxa (anuran)-specific
neurotoxins in the secretion as well as mammalian
responses to other components such as proteolytic hemor-
rhagins, myotoxins, etc. The occurrence of prey-specific
toxins in Duvernoy’s secretion from Heterodon sp. has been
considered by several researchers (e.g. Minton and Minton,
1980; Young, 1992). Recently, avian and/or saurian-specific
toxins have been characterized from the Duvernoy’s secre-
tions of the mangrove snake, Boiga dendrophila (Pawlak
et al., 2006) and brown tree snake, B. irregularis (Pawlak
et al., 2009).
Type I hypersensitivity to snake venoms is a recognized
consequence of sensitization by previous envenomings,
frequent handling of venomous snakes, and repetitive
exposure to crude or lyophilized venoms (Reimers et al.,
2000; Medeiros et al., 2007; Malina et al., 2008). Individual
history of atopy probably is a contributing factor (Medeiros
et al., 2007). The potential development of hypersensitivity
to antigens shared among colubrid (or, possibly, among
many ophidian species) oral secretions may play an
important contributing role in medically significant bites
from Heterodon sp. and other colubrids. Assessment of
serum IgE levels and clinical responsiveness to corticoste-
roid regimens during such episodes may clarify the etiology
of these symptoms.
3.2. Features of previously reported cases: does the feeding
response influence the severity of medically significant
Heterodon bites?
The present case is congruous with previously docu-
mented reports suggesting that some bites from H. nasicus
may result in medically significant sequelae (Hornfeldt and
Keyler, 1987). Edema, ecchymoses and, occasionally,
persistent discharge from tooth punctures are sequelae
common in most reports of medically significant Heterodon
bites. Table 1 summarizes previously reported cases of
Heterodon bites.
As suggested from the history of some cases of Hetero-
don sp. bites, elicitation of a feeding response may result in
a sustained grip and, possibly, a greater engagement of the
posterior maxillary teeth. This probably increases the
likelihood of introduction of a larger volume of Duvernoy’s
secretion into the wound and may result in a clinically
significant bite. Rapid (i.e. quick release) bites with subse-
quent envenoming by ‘‘rear-fanged’’ snakes certainly occur
(Warrell, 2004). However, available well-documented cases
suggest that these are less common than those caused by
a protracted bite.
3.3. Conclusions, additional considerations and some
recommendations for management of medically significant
Heterodon bites
In summary, we have described a bite inflicted by a H.
nasicus that resulted in significant local morbidity. Hognose
snakes are phlegmatic and mild captives and cases such as
described here are rare. Therefore, these snakes should not
be viewed as venomous or dangerous, nor subjected to
regulation. It is advisable that captive specimens be
handled with care (especially when offered food) and any
medically significant bites be promptly reviewed by
a qualified health professional. Similarly, a provisional
caution is warranted in regard to the South American
hognose snakes (Lystrophis sp). Although there are anec-
dotal reports regarding mild local effects resulting from
bites inflicted by Lystrophis sp. (Warrell, 2004), there are no
data regarding specific toxicity of oral secretions from these
snakes. Kardong (personal communication) has dissected
Duvernoy’s glands from Lystrophis sp. It is likely that all
members of the genus have Duvernoy’s glands and produce
secretion of unknown potency. Many Lystrophis sp. are
attractively tri-colored and are reasonably popular in
private collections.
Although there is no specific treatment (other than
wound care and symptomatic management) recom-
mended for medically significant bites inflicted by Hetero-
don sp., we recommend that patients bitten by these and
other colubrids of unknown medical importance be
observed in a medical facility as long as necessary to rule
out development of any significant local or systemic effects
following a bite. Comprehensive laboratory testing
(including differential blood count, coagulation panel,
creatine kinase and comprehensive metabolic panel)
should be performed along with meticulous wound care.
The medical team should remain aware of the possibility of
Type I hypersensitivity in patients bitten by any ophidian
species including Heterodon. Assessment of this risk should
be performed by procurement of a careful history regarding
handling of snakes, cleaning cages of captive specimens,
handling shed skins and documentation of previous bites
by venomous and non-venomous species.
Referral should be considered as required, and close
follow-up is essential. Use of prophylactic antibiotics in
most snakebites is not supported by available evidence
(LoVecchio et al., 2002; White and Dart, 2008), however, in
the case of secondary infection, a broad spectrum antibiotic
with
b
-lactamase inhibitor (e.g. amoxicillin/clavulanate,
875 mg/125 mg, twice per day for 7 days) may be
prescribed. Penicillin allergic patients may be treated with
doxycycline, 100 mg, twice per day for 10 days or clinda-
mycin, 150–400 mg (dose dependent on severity of the
infection), four times per day for 7 days. Due to the risk of
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354–360358

Clostridium difficile colitis, clindamycin should be avoided
in elderly patients or those who have recently taken other
antibiotics (or who have been recently hospitalized).
Anaerobic coverage (and some protection against C. difficile
colitis) can be addressed with provision of metronidazole,
500 mg, three times per day for 7 days. Consultation with
a physician or knowledgeable health professional familiar
with clinical toxinology is recommended. Importantly, all
medically significant bites inflicted by any colubrid snake
should be carefully clinically documented with precise
identification of the offending species and, preferably, in
cases where the snake has been sacrificed, deposition of the
specimen in a recognized institution accompanied by
accurate provenance.
Acknowledgements
We thank A.B. Sheldon for the photo of H. nasicus and
Prof. Ken Kardong, School of Biological Sciences, Wash-
ington State University, Pullman, Washington, for his
comments and data from dissections of Lystrophis sp. and H.
platirhinos. The comments of Prof. Julian White and Mr.
Alan Staples are gratefully acknowledged.
Conflicts of interest
I have no competing interests concerning the submitted
manuscript or components of the manuscript.
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Table 1
Previously reported cases of Heterodon bites.
Species Size of offending
specimen (cm)
Age of
victim (years)
Reported symptoms/signs
a
Review by health
professional?
Time to resolution
of symptoms
Reference
Heterodon nasicus 53 NR E, T, BL, ‘‘burning’’ No Approx. 2 weeks Bragg (1960)
Heterodon platirhinos
b
89 16 P (‘‘burning’’), E, N, BL,
persistent ER, WD
No 4 months Grogan (1974)
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 specifically bite the victim. Rather, several teeth were imbedded in the skin while the specimen was feigning death with
mouth agape.
S.A. Weinstein, D.E. Keyler / Toxicon 54 (2009) 354–360 359

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