572566

research-article2015

IJI0010.1177/0394632015572566International Journal of Immunopathology and PharmacologyPagan et al.

Letter to the editor

Snake (Vipera berus) bite: The cause

of severe anaphylactic shock and
hepatocellular injury

International Journal of
Immunopathology and Pharmacology
2015, Vol. 28(1) 119121
The Author(s) 2015
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0394632015572566
iji.sagepub.com

K Pagan, A Kumiski, A Janik, M Gotz-bikowska and Z Bartuzi

Abstract
Vipera berus bites lead to a variety of clinical manifestations. Local swelling, coagulopathy, nephrotoxicity, cardiac effects
and myotoxicity are known to be associated with envenoming by a viper bite. Although a variety of clinical manifestations
have been reported in viper bite cases, anaphylactic reactions and liver injury events have not been described. We report
a unique case of an anaphylaxis and transitional liver cell injury due to a Vipera berus bite in the case of a 58-year-old
man with no past history suggestive of allergy and liver disease. These observations need to be further explored with
laboratory studies to identify the venom components which could have pre-disposed the patient to the development of
these complications.
Keywords
anaphylaxis, liver injury, Vipera berus
Date received: 5 September 2014; accepted: 15 December 2014

Snake bites are responsible for as many as 94,000

deaths worldwide every year. In European countries the fatality rate is in the range of 0.11.8%
and mortality is established at 0.00010.29 per
100,000 inhabitants. The most venomous snake
found in Poland is Vipera berus. It has a very
characteristic zig zag along the back. Vipera berus
hibernates in winter and bites most frequently in
June, July or August. Its venom is composed of a
mixture of proteolytic enzymes like phospholipase A2 (PLA2), hialuronidase, toxic peptides,
amino acids, neurotransmitters and carbohydrates. This venom complex results principally in
cytotoxicity and haemotoxocity. Venom may disrupt endothelial cell linings, cause rhabdomyolysis and lead to liver and kidney failure. In addition,
cardiac effects such as cardiotoxicity, ST segment
changes, infarction of the heart and block have
been described.1
We report a case of envenoming by a Vipera
berus that involved a severe collapse and a hepatotoxicity in the first days of March.

Case report
A 58-year-old man was admitted to the Emergency
Department at 15:40 on Saturday 8 March following a Vipera berus bite to his left middle finger
(Figure 1). He had been bitten at 15:00 on the same
day while he was gardening. The incident happened during the pruning of a hedgerow. The victim reported no previous snake bites and no history
of increased alcohol consumption, while viral
hepatitis markers were all negative. The patient
reported hymenoptera stings in the past history.
About 3 min after he had been bitten the finger
puffed up and began to sting at the bite site. Upon
Department of Allergology, Clinical Immunology and Internal Diseases
Collegium Medicum Bydgoszcz, Nicolaus Copernicus University in
Toru, Collegium Medicum of L Rydygier, Bydgoszcz, Poland
Corresponding author:
Krzysztof Pagan, Department of Allergology, Nicolaus Copernicus
University, Collegium Medicum in Bydgoszcz, Clinical Immunology and
Internal Diseases, Ujejskiego 75, 85-168 Bydgoszcz, Poland.
Email: palgank@wp.pl

120

International Journal of Immunopathology and Pharmacology 28(1)

Figure 1.The Vipera berus bite left the middle finger with two
fang marks.

leukocytosis with a total white blood cell count of

21.58 G/L with 88% neutrophils (Table 1). Blood
urea and serum electrolyte values were within the
reference range throughout. Other laboratory parameters revealed elevated D-dimer but other coagulation parameters were normal. For fear that the subject
could develop thrombosis, he received Nadroparinum
0.3 s. c. daily. On the seventh day of the clinical treatment the liver enzyme elevation was observed.
The aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGTP) were increased (Figure 3). The
infectious hepatitis screening panel was negative.
Additional laboratory values showed total IgE 69,91
IU/L and negative specific IgE (ImmunoCAP) to a
combination of common allergens. To establish other
possible immunological changes associated with
envenomation a flow cytometry test was performed.
The populations and subpopulations of the peripheral
blood leukocytes were in the recommended reference
range. The electrocardiogram, the chest radiography
and the ultrasound (USG) were not contributory. The
general condition of the patient improved gradually
and he was discharged after 11 days in hospital.
There were no complications following the check-up
which was performed 1 month after the bite.

Discussion

Figure 2. Erythema, bruising and oedema of the left forearm

and arm after the Vipera berus bite.

admission to our hospital the subject felt weakness

and the hand appeared swollen. He was profoundly
nauseated and he had five attacks of profuse diarrhoea. At the Emergency Depart-ment he received
antivenom against V. berus (Antitoxinum vipericum,
Biomed, Warsaw, Poland) 500 units i.m. and he was
transferred to our Clinic. On admission, the patient
was conscious and responded to verbal commands;
blood pressure was 63/40 mmHg and pulse rate was
120/min. He was treated immediately with adrenalin
0.5 mg i.m., Dexamethasoni natrii phosphas 8 mg
(i.v.), Clemastinum 2 mg i.v. and a normal saline
slow drip. Intravenous Cefotaxime 1.5 g was given
every 12 h as a prophylactic antibiotic. Over the next
2 days in hospital, he developed painful swelling and
redness of the whole left forearm stretching up to
the lower part of the upper arm (Figure 2). During
hospitalization the full blood count showed marked

Snake bites are an environmental hazard, particularly in rural areas, causing significant morbidity
and mortality. The incidence and frequency of
snake bites vary in different regions and a dependence on climate and distribution of snakes is
observed. In Poland snake bites are rarely reported.
This particular patients case is worth reporting
since there had been no report of a case of anaphylactic reaction and hepatocellular injury associated with a snake bite. The main complications
after snake bites are coagulopathy, thrombocytopenia, bleeding, anaemia, renal failure, acute or
chronic hypopituitarism and cardiac disorders.2
The patient described here manifested symptoms
of anaphylaxis. There are several putative mechanisms by which anaphylaxis may occur in envenomation by a snake. Anaphylaxis can be mediated
through IgE-dependent and IgE-independent
release of mediators from mast cells and basophils.3 Snake venom contains phospholipase A2,
an enzyme present in the Viperidae snake family
and even other species like hymenoptera which
exhibit a potent anaphylactic effect. Our patient

121

Pagan et al.
Table 1. Morphology of the blood cells.

08/03/2014
09/03/2014
10/03/2014
12/03/2014
14/03/2014
17/03/2014

WBC
(G/L)

RBC
(T/L)

HGB
(g/dl)

PLT
(G/L)

9.69
13.72
21.58
12.72
15.30
10.12

5.61
4.81
4.59
4.84
5.3
5.14

17.0
14.6
14.3
14.8
16.2
15.6

249
217
209
187
222
213

Acvity
(U/l)

NEUT
(%)

88.0
80.0
75.6
46.2

LYMPH
(%)

6,4
13.0
14.6
39.5

MONO
(%)

4.7
5.8
6.8
8.4

EOS
(%)

BASO
(%)

0
0
0.2
3.0

0
0.1
0.9
0.9

450
400
350
300
250

GGTP

200

ALT
AST

150
100
50
0

14.03.2014

15.03.2014

17.03.2014

18.03.2014

Figure 3. Liver enzyme activity GGTP, ALT and AST during the patients hospitalisation.

was stung by hymenoptera, so the anaphylaxis

may be the result of cross-reactivity between viper
venom and hymenoptera. The other cause of hypotension might be adverse reactions to the antivenom given. In this case, laboratory tests did not
confirm allergic sensitisation. In our case the
involvement of alternative pathways of anaphylaxis is also most probable.
Liver injury following viper bites has not been
reported in the literature. Clinical observations
have suggested that dogs and experimental animals
like mice could develop hepatic disease after snake
envenomings.4,5 The reported case represents
increased levels for ALT, AST and GGT (Figure 3).
Envenomation following bites by Vipera berus can
result in hepatocellular injury. These may develop
slowly over several days.
Another effect of constituents of venom is
locoregional impact on the soft tissues. The
phospholipase A2 and other cytotoxic proteins
of the venom attack endothelial cells and account
for the oedema, pain and inflammation.
In conclusion, clinicians should acknowledge
that snake bite is an uncommon condition, but
requires vigilance with regard to systemic effects
like anaphylaxis and transitional liver cell injury.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publication
of this article.
Funding
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
References
1. Garkowski A, Czupryna P, Zajkowska A, et al. (2012)
Vipera berus bites in Eastern Poland: A retrospective
analysis of 15 case studies. Annals of Agricultural and
Environmental Medicine 19: 793797.
2. Bandyopadhyay SK, Bandyopadhyay R, Dutta A,
et al. (2012) Hypopituitarism following poisonous
viper bite. Journal of the Indian Medical Association
110: 120122.
3. Galli SJ and Tsai M (2013) IgE and mast cells in allergic disease. Natural Medicine 18: 693704.
4. Lervik JB, Lilliehk I and Frendin JH (2010) Clinical
and biochemical changes in 53 Swedish dogs bitten
by the European adderVipera berus. Acta Veterinaria
Scandinavica 52: 26.
5. Silva A, Gunawardena P, Weilgama D, et al. (2012)
Comparative in-vivo toxicity of venoms from South
Asian hump-nosed pit vipers (Viperidae: Crotalinae:
Hypnale). BMC Research Notes 5: 471.