Snake ( Vipera berus ) bite: The cause of severe anaphylactic shock and hepatocellular injury

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.

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 0.1–1.8% and mortality is established at 0.0001–0.29 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.

Figure 1.

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

About 3 min after he had been bitten the finger puffed up and began to sting at the bite site. Upon 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 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.

Figure 2.

Erythema, bruising and oedema of the left forearm and arm after the Vipera berus bite.

Table 1.

Morphology of the blood cells.

	WBC (G/L)	RBC (T/L)	HGB (g/dl)	PLT (G/L)	NEUT (%)	LYMPH (%)	MONO (%)	EOS (%)	BASO (%)
08/03/2014	9.69	5.61	17.0	249
09/03/2014	13.72	4.81	14.6	217
10/03/2014	21.58	4.59	14.3	209	88.0	6,4	4.7	0	0
12/03/2014	12.72	4.84	14.8	187	80.0	13.0	5.8	0	0.1
14/03/2014	15.30	5.3	16.2	222	75.6	14.6	6.8	0.2	0.9
17/03/2014	10.12	5.14	15.6	213	46.2	39.5	8.4	3.0	0.9

Figure 3.

Liver enzyme activity GGTP, ALT and AST during the patient’s hospitalisation.

Discussion

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 patient’s 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 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 anti-venom 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.