Case Report: An unusual case of bee envenomation presenting with acute kidney injury, cavernous venous thrombosis and multiple episodes of convulsions

Envenomation by bees is common world wide and especially in the tropics. The commonest manifestations are local reactions for example vomiting, diarrheoa, generalized oedema and hypotension. On rare occasions, you may get renal, cardiovascular and central nervous complication. We present a case of an 8-year-old boy who developed acute kidney injury, cavernous sinus thrombosis and multiple convulsions but recovered without sequelae.


Introduction
Envenomation by bees is common world wide and especially in the tropics. The commonest manifestations are local reactions for example vomiting, diarrheoa, generalized oedema and hypotension. On rare occasions, you may get renal, cardiovascular and central nervous complication. We present a case of an 8-year-old boy who developed acute kidney injury, cavernous sinus thrombosis and multiple convulsions but recovered without sequelae. unit with history of bee bite on the face one week prior to admission at a private facility. He was reported to have been stung x3 by bees. Child was referred and admitted to a private facility on 14th February 2017, where he was found to have generalized oedema, vomiting, cough but no fever.
UECs: see the serial levels below but all were deranged and consistent with AKI.
Chest had bilateral rhonchi but no crepitations.

Discussion
We describe a complicated case of a young boy who had few bee bites and eventually developed severe manifestations with acute kidney injury, multiple brain infarcts, venous thrombosis and convulsions.
The prevalence of insect sting allergy is estimated to be between 0.5% -3%, and people who have previously experienced generalized allergic insect sting reactions are at increased risk for reactions from future stings [1]. The allergic reaction can be triggered by a single sting, and the greater the number of stings, the worse the prognosis because multiple stings lead to inoculation of a higher amount of venom [2]. This was unusual; most cases have been described after multiple envenomation and it is reported that you need about 1500 bites for a 75 kg person to reach a threshold to give you the manifestations we saw in this child [3]. He had mild venom exposure (<1 sting/kg body weight) which usually has cutaneous manifestations only, but his symptomatology was for high venom exposure (4 -9 stings/kg body weight) [4]. Fewer bee stings are normally not associated with much pathology unless a patient develops anaphylaxis, as is this case.
Bee venom contains peptides, proteins and vasoactive amines for example histamine, acetylcholine, norepinephrine, dopamine and 5-hydroxytryptamine which are thought to be responsible for some of the allergic manifestations [1]. Melittin is the main peptide, and it is the main lethal component of bee venom [2].
The most common manifestations associated with fewer stings include pruritis, hives, oedema, erythema, dizziness, dyspnoea and occasionally anaphylaxis. 5 Multiple bee stings may be associated with various organ dysfunctions, namely [1,4]

Acute kidney injury
AKI caused by bee stings are often accompanied with multiple organ dysfunction syndrome (MODS), with the mortality rate ranging from 9.3% to 60%. It is usually observed 48-72 hours after the accident, just like it happened in this case [6].
The mechanism through which renal damage occurs following bee venom inoculation is not fully understood [2,6]. Multiple factors, such as intravascular hemolysis, rhabdomyolysis, hypotension, low cardiac output, and direct toxicity of the venom components to the renal tubules by possible melittin-induced apoptosis, may contribute to the pathophysiology [7]. Intravascular haemolysis and rhabdomyolysis: peptides such as melittin, apalim and phospholipase A can provoke these processes, and they are demonstrated by elevated serum levels of indirect bilirubin and creatine kinase.
Rhabdomyolysis causes renal vasoconstriction, formation of intratubular deposits of myoglobin, direct cytotoxicity of myoglobin to the renal tubule cell and DIC, which leads to the release of thromboplastin, thus formation of microthrombi in the glomeruli. All these consequently cause reduced Glomerular Filtration Rate (GFR).
Hypotension: The same peptides mentioned above, amongst others, can induce the release of several other mediators, such as histamine, serotonin, bradykinin and prostaglandins, which are vasoactive and may lead to a reduction in systemic blood pressure.
In addition, melittin has depressive and cardiotoxic effects; in large quantities, it causes cardiac spasm and cardiovascular collapse. Apamin acts as a neurotoxin with motor action, causing systemic vasodilation. Both these substances generate severe hypotension and increased heart rate.
Renal hypoperfusion activates the renin-angiotensinaldosterone system, leading to vasoconstriction of both afferent and efferent arterioles, worsening the GFR; thus, ischaemia and development of Acute Tubular Necrosis (ATN).

Brain infarcts
An MRI scan of the brain, done when the child began convulsing, revealed bilateral frontoparietal and occipitoparietal laminar infarcts. Neurological manifestations of bee stings are rare [8]. The exact pathophysiology explaining strokes due to honey bee bite is still unknown. Possible causes include hypotension inducing cerebral ischaemia, exogenous adrenaline, and thromboxane and leukotrienes within the venom, causing vasoconstriction, platelet aggregation secondary to various compounds released, cerebral embolism, hypertensive haemorrhage and DIC [8,9].

Cavernous Sinus Thrombosis (CST)
The MRI scan also showed venous sinus thrombosis.
Unfortunately, there is paucity of data in the incidence and possible pathophysiology that may lead to this following bee venom inoculation. One previous case of a 58-year-old man who was bitten by a bee on his left upper lip, and subsequently developed CST 48 hours later, is found in literature [10]. Possible

Immediate management
This should consist of epinephrine 0.01mg/kg of 1:1000.

Consent to publish
Verbal informed consent was obtained from the parent of the patient for publication of this case.