A 5-year-old male castrated Border Terrier presented to the Animal Emergency Centre following massive bee envenomation (exposure to toxin). His owners had come home to find him distressed and surrounded by multiple dead and dying bees.

Diagnosis

Upon presentation, the dog was mildly obtunded (in a state of lethargy), panting, and with injected mucous membranes. The rest of the vital parameters were within normal limits. He had mild facial edema that was worse in the peri-ocular area (around the eyes). Over 100 bee stings were visibly attached to the dog’s skin over the entire body and head.

Subcutaneous chlorpheniramine (0.4 mg/kg) and dexamethasone (0.15 mg/kg) were administered upon arrival. Intravenous fluid therapy with lactated Ringer’s solution at twice the maintenance rate was started. Intravenous diazepam (0.4 mg/kg) and buprenorphine (0.02 mg/kg) were given for sedation and pain relief to allow the removal of over 100 bee stings.

After seven hours of hospitalisation, the dog became increasingly obtunded, still with injected mucous membranes and showing signs of muscle weakness. He started to regurgitate, had absent gut sounds, and was inappetant. Pigmenturia was noted.

A complete blood cell count, serum biochemistry, blood gases, serum electrolytes, acid-base balance, clotting times, packed cell volume and total protein were performed. Abnormal results were a blood glucose of 6.8 mmol/L (RR: 3.9-6.1 mmol/L), aspartate transaminase >1000 U/L (RR: <50 U/L), creatine kinase >40,000 U/L (RR: 80-375 U/L) and activated partial thromboplastin time of 119.5 seconds (RR: 72-102 seconds). A urine specific gravity was 1.052.

An abdominally focused ultrasound looking for free abdominal fluid was performed and revealed no free abdominal fluid. The gall bladder wall was normal in appearance and thickness. A diagnosis of massive bee envenomation was made, with secondary organ damage to the neurological, muscular, hepatic and gastrointestinal systems. Anaphylactic shock was not present.

Further treatment was provided with maropitant (1 mg/kg subcutaneously once daily), metoclopramide (0.5 mg/kg intravenous bolus followed by a constant rate infusion at 1mg/kg/d) and pantoprazole (1 mg/kg intravenously every 24 hours). Analgesia was changed from buprenorphine to methadone (0.2 mg/kg intravenously every 4 hours).

On the second day of hospitalisation the dog remained ataxic, being especially weak in the pelvic limbs, and the facial swelling was still present. He was cardiovascularly stable although with vitals within normal parameters. The chlorpheniramine and dexamethasone injections were repeated. Analgesia was changed to a 50 µg/h fentanyl patch. By the end of the second day in hospital, the dog’s clinical condition started to improve, with resolution of the facial swelling, weakness, and pigmenturia. Serum creatine kinase had reduced to 2965 U/L indicating no ongoing muscle damage was occurring. He was eating with no further gastrointestinal signs and was discharged home to continue the recovery.

Discussion

It is common for our team at the Animal Emergency Centre to see animals with local hypersensitivity reactions and anaphylaxis from insect envenomations. However, massive bee envenomation is rare. Reports from the USA and Canada have commented on an increase in the number of massive bee envenomation cases due to a dramatic rise in the number of Africanised bees in some areas. These cases have improved our knowledge of the systemic effects of bee envenomation in dogs.

It is important to note that this animal had systemic signs of bee envenomation, however, there was no evidence of anaphylaxis. Anaphylaxis is caused by the release of mediators from mast cells that are triggered by either immunologic or non-immunologic stimulation. It is these mediators that bring about the life-threatening consequences of anaphylaxis including respiratory distress, hypotension, and dysrhythmias. Envenomation, on the other hand, refers to the injection of venom by bite or stinging apparatus. The systemic effects seen in envenomation are due to the venom components themselves.

Bee venom is composed of numerous components that can cause a wide spectrum of systemic effects including neurotoxicity, rhabdomyolysis, intravascular haemolysis, liver necrosis, haematemesis, haematochezia, acute kidney injury, acute lung injury, coagulopathy, and thrombocytopenia.2,3,4 If death occurs it is usually because of cardiovascular collapse, myocardial necrosis and infarction or kidney failure. Two of the main components that play an active part in the above systemic effects are melittin (50% of venom dry weight) and phospholipase A2 (12% of venom dry weight).

Both substances cause rhabdomyolysis, hemolysis, and acute kidney damage by specifically acting on the kidney tubules.1,5,6 The primary effect of phospholipase A2 is cell lysis. It also increases the production of arachidonic acid which promotes inflammatory responses throughout the body. Melittin is a Na+-K+-ATPase and H+-K+-ATPase pump inhibitor leading to increased cell membrane permeability. Melittin also causes histamine release, leads to the development of pain and itching at the sting site, and aids in the venoms’ spread throughout the body through an increase in capillary permeability. It also has direct cytotoxic effects.

An animal’s clinical signs following bee envenomation varies with the type of venom, the victim’s sensitivity, the number and location of stings, and the amount of venom delivered. Commonly animals will be stung of the face, ears or limbs as these areas are most exposed. The estimated lethal dose in mammals is 20 stings/kg however even a single sting can lead to death.

Treatment should include removal of as many of the stings as possible to reduce further venom spread and this may have contributed to the survival of the animal reported here.9 Removal of large numbers of stings usually requires sedation. Uncomplicated case treatment should include corticosteroids and antihistamines, cool compression of the swellings, +/- topical lidocaine and opioid analgesia. Because all animals that are stung by bees can have life-threatening reactions, close observation should occur for 12-24 hours post envenomation. Acute onset anaphylactic reactions are not influenced by the dose of venom and usually occur within 10 minutes of envenomation.5 If there are indications of anaphylaxis on physical examination, the above treatment should be given, along with supportive care through intravenous fluids as indicated and adrenaline administration (0.0025-0.005 mg/kg IV followed by a CRI at 0.005 mg/kg/min). Patients with rhabdomyolysis should have intravenous fluid diuresis to protect the kidneys from injury secondary to myoglobinuria.10 If an animal does develop acute kidney injury and is anuric, then dialysis may be required. Gastrointestinal protectants will be required in some patients. Monitoring of serum biochemistry, hematology and coagulation profiles are recommended.

References

1. Grisotto LS, Mendes GE, Castro I, Baptista MA, Alves VA, Yu L, Burdmann EA. Mechanisms of bee venom-induced acute renal failure. Toxicon 2006, 48(1):44-54.

2. Mathew A, Chrispal A, David T. Acute myocardial injury and rhabdomyolysis caused by multiple bee stings. J Assoc Physicians India 2011, 59:518-20.

3. Akdur O, Can S, Afacan G. Rhabdomyolysis secondary to bee sting. Case Rep Emerg Med 2013;2013:258421.

4. Nakamura RK, Fenty RK, Bianco D. Presumptive immune-mediated thrombocytopenia secondary to massive Africanized bee envenomation in a dog. J Vet Emerg Crit Care 2013, 23(6): 652–656.

5. Fitzgerald KT, Flood AA. Hymenoptera stings. Clin Tech Small Anim Pract 2006, 21(4):194-204.

6. Odinaka KK, Achigbu K, Ike I, Iregbu F. Bee sting envenomation resulting in gross haematuria in an eight-year-old Nigerian male with sickle cell anaemia: A case report. Niger Med J 2015 Jan-Feb;56(1):69-70.

7. Vetter RS, Visscher PK, Camazine S. Mass envenomations by honey bees and wasps. West J Med 1999, 170(4):223-227.

8. Schmidt OJ, Hassen LVB. When Africanized bees attack: what you and your clients should know. Vet Med 1996, 91:923-928.

9. Muhammad G, Saqib M, Mallick SH. Honey-bee stinging (apisination): what the medical and veterinary professionals ought to know? Pakistan Vet J 2000, 20:209-211.

10. George P, Pawar B, Calton N, Mathew P. Wasp sting: an unusual fatal outcome. Saudi Journal of Kidney Diseases and Transplantation. 2008;19(6):969–972.