Acute Neurological and Respiratory Complications Induced by Wasp Stings: A Case Report

Introduction

In Sichuan, China, honeybee and wasp stings occur frequently in summer and autumn. Wasps, hornets, and bees are classified biologically into the order Hymenoptera. The toxins in wasp venom contain biologically active enzymes, biogenic amines, lipids, and amino acids, which are strong animal allergens. They usually cause local reactions and anaphylaxis, and urgent hospitalization is rarely required. The major complications include hemolysis, rhabdomyolysis, acute renal failure, and hepatic injury [1–3]. However, neurological and respiratory manifestations such as ischemic stroke and acute respiratory distress syndrome (ARDS) following bee stings are rare. The underlying pathogenesis remains unclear and appears to be multifactorial [4,5]. We present the case of a 56-year-old woman who developed ARDS, acute kidney injury (AKI), and cerebral infarction following an attack by numerous wasps.

We retrospectively analyzed the case of a patient with multiple wasp stings who was admitted to the Affiliated Hospital of North Sichuan Medical College on September 7, 2021. Symptoms, laboratory findings, and dynamic and comprehensive imaging examinations were also assessed. In addition, we collected additional data on treatments, outcomes, and related follow-up data. This report aims to enhance clinical awareness of the early recognition and treatment of rare complications that can arise following wasp stings.

Case Report

A 56-year-old woman was attacked by numerous wasps while working in a farm field. Multiple swelling sites on her head, face, upper limbs, and trunk were associated with pain and redness. She also experienced nausea and mild headache. The pain was slightly alleviated after treatment at a local hospital. Seven hours later, she was transferred to the Emergency Department of the Affiliated Hospital of North Sichuan Medical College, with soy-sauce-colored urine.

She had hypertension and had been taking antihypertensive drugs irregularly over the past 30 years.

She was conscious on admission, with body temperature 36.8°C, pulse rate 96 beats/minute, respiratory rate 26 beats/minute, and blood pressure 148/124 mmHg. Redness, swelling, and pain were observed on the face and upper limbs. Neurological examination showed normal limb function with a power of 5 MRC (Medical Research Council) grade, normal muscular tone and no sensory abnormalities. Pathological signs were negative. Laboratory examinations revealed a white blood cell (WBC) count of 31.59×109/L with 94.5% neutrophils. Her high-sensitivity C-reactive protein was 54.83 mg/L, D-dimer assay was 5.79, N-terminal pro B-type natriuretic peptide was 24 188.0 pg/mL, plasma prothrombin time was 14.2 seconds, the international normalized ratio of prothrombin was 1.21, and fibrin/fibrinogen degradation products were 13.70 μg/mL, all of which were significantly elevated. In addition, the laboratory examinations also revealed elevated total bilirubin 83.8 μmol/L, direct bilirubin 2.5 umol/L, aspartate aminotransferase (AST) 2125 U/L, and alanine aminotransferase (ALT) 383 U/L, as well as high lactate dehydrogenase (LDH) (5293 U/L) and serum creatinine (270.0 μmol/L). Urinalysis revealed 3+ proteinuria and 3+ occult blood, with many erythrocytes in a high-power field. ECG and echocardiographic findings were normal. No evidence of thrombosis was detected in the vascular color Doppler ultrasound of the upper and lower extremities. The main treatment for the patient included intravenous methylprednisolone at a dose of 200 mg/day for 3 days, plasma exchange 3 times, and continuous renal replacement therapy (continuous venous hemodiafiltration, CVVHDF) 8 times.

Her condition worsened 11 hours after admission and her blood pressure decreased to 64/44 mmHg. Vasopressors were used to maintain the mean arterial blood pressure above 65 mmHg, which was stopped after 24 h. After 15 h of follow-up, she developed severe respiratory dyspnea, and her fingertip oxygen saturation declined to 75%. Mask oxygen inspiration was performed immediately, but the oxygen saturation remained at approximately 85%. Arterial blood gas analysis revealed a pH of 7.376, PO2 of 56.3, PCO2 of 26.4, and oxygenation index of 190. Endotracheal intubation and invasive ventilation were performed simultaneously. A chest computed tomography (CT) scan revealed non-homogeneous lung transparency and exudative lesions, and there was a small amount of effusion in the right pleural cavity accompanied by right pleural thickening (Figure 1). Changes in oxygen index were recorded (Figure 2). One week later, her condition markedly improved and the tracheal tube was removed.

However, left hemiparesis was noticed on the 8th day after admission. Her muscle strength in the left upper and lower limbs was grade 3 according to the MRC grade. She had left hypoesthesia and a positive pyramidal tract sign. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain showed acute infarction in the right insular lobe, external capsule, and basal ganglia with no midline shift or mass effect, and no obvious intracranial vascular stenosis (Figure 3). She was then administered conventional treatments for cerebral infarction, including antiplatelet aggregation (aspirin 100 mg qd) and lipid-lowering (atorvastatin 10 mg qd) and rehabilitation therapies. After 4 days of treatment, the neurological conditions were ameliorated. Her muscle strength in the left upper and lower limbs was grade 4. Left hypoesthesia persisted but was restored by the 13th day. She was then transferred from the EICU to the emergency ward. Subsequently, skull MRI and chest computed tomography (CT) findings were reviewed. There were no obvious changes in the intracranial lesions and most of the exudative pulmonary lesions had faded. She was discharged 26 days after admission. At follow-ups 3 and 6 months after discharge, her left limb strength recovered to grade 4+ according to the MRC grade (Figure 4).

Discussion

Wasp stings are common. Wasps belong to the order Hymenoptera, suborder Apocrita, and family Vespidae [6]. The severity and duration of clinical manifestations following wasp stings can vary among patients and at different occurrences in the same individual [7]. Most cases appear only as local reactions, and some may develop serious anaphylaxis [8]. Patients who recover from anaphylaxis usually do not develop further symptoms [9]. According to reports from the United States and Europe, the incidence of systemic reactions after a bee sting is mentioned [10]. Rarely, patients develop organ dysfunction such as AKI, cardiac dysfunction including myocardial infarction, arrhythmias, or myocarditis, etc. [11–13].

Wasp/bee-associated stroke is also believed to be uncommon and can present as a cerebral hemorrhagic or ischemic stroke. In 1962, Day [14] first reported a patient who presented with hemorrhagic cerebral infarction following a wasp sting. Over the past 30 years, wasp/bee sting-related cerebral infarction cases have been reported in succession, but less than one per year [15–28]. These cases have mainly been reported in the United States [14,20–24] and India [15–19]. The exact etiology and pathogenesis of cerebral infarction following a bee sting are not completely clear, but may be related to the following factors. The venom mainly consists of 4 basic parts: (A) enzymes such as phospholipase A2 and hyaluronidase; (B) peptides such as melittin and chemotactic peptides; (C) amines such as histamine, serotonin, and catecholamines; and (D) mastoparan, kinins, apamine, acetylcholine, antigen 5, and neurotoxic cynines [29] Phospholipases in wasp venom may cause allergic reactions, leading to hypotension and reduced cerebral perfusion [6]. Moreover, the immunoglobulin E response may trigger anaphylactic shock, leading to cerebral hypoperfusion. If shock is not corrected in a timely manner, cerebral infarction may occur. Additionally, wasp venom activates thromboxane A2 and phospholipase, resulting in a hypercoagulable state and platelet aggregation [9]. Simultaneously, histamine and leukotriene released from activated mast cells may initiate small vessel inflammatory reactions, prompting the motivation and aggregation of platelets, giving rise to vaso-occlusion and cerebral infarction [6]. In addition, histamine and leukotrienes can induce vasospasm and vasoconstriction of the vasculature, ultimately leading to cerebral infarction [22]. However, the formed immune complex deposited on the cerebral vasculature causes occlusion of the cerebral small vessels and subsequently leads to multiple cerebral infarctions. The venom can also directly act on vascular smooth muscle cells, leading to vascular spasms, causing reversible occlusion of blood vessels, and ultimately leading to cerebral infarction. In this study, cerebral infarction may have partly resulted from a systemic immune-mediated reaction. Allergic hypotension resulting from an allergic reaction leads to cerebral perfusion reduction and ischemia, eventually leading to a stroke. Systemic immune-mediated reactions initiate small vessel inflammatory reactions, stimulate the motivation and aggregation of platelets, give rise to vaso-occlusion, and cause cerebral infarctions.

ARDS is characterized by bilateral chest radiographic opacities that are hardly rectified and severe hypoxemia [30]. Few cases of ARDS following bee stings have been reported, and its pathogenesis remains unclear. The key component of bee venom, mastoparan, can enhance histamine release from mast cells [2]. Histamine and other inflammatory mediators released from activated mast cells may increase the permeability of the pulmonary microvasculature, resulting in fluid spilling into the alveolar cavity and acute pulmonary edema [31]. The development of pulmonary edema requires several hours. However, fluid shifts due to immediate anaphylaxis or toxic reactions after bee stings may have started early. This leads to the development of acute pulmonary edema and causes a chain of events, such as prolonged hypoxemia and metabolic acidosis. ARDS may eventually develop [32]. Symptoms of acute pulmonary edema do not appear at an early stage. In this study, the patient initially presented with an increased respiratory rate. However, her condition worsened, and had severe respiratory dyspnea. Fingertip oxygen saturation continuously declined, and the oxygen index was below 200. Chest CT showed inhomogeneous lung transparency and exudative lesions.

AKI is a serious complication associated with multiple wasp stings. Its incidence is 30–50%, with high mortality [33]. Bee venom peptide accounts for the largest proportion of bee and cooperates with phospholipase A2 and hyaluronidase to damage cell membranes. It causes hemolysis, rhabdomyolysis, and liver and kidney dysfunction [34]. Patients with rhabdomyolysis after a bee sting are more likely to develop AKI. Currently, the pathophysiological mechanisms underlying wasp sting-related kidney injuries remain unclear. Wasp-sting-related AKI may result from direct nephrotoxic effects of the venom, secondary to intravascular hemolysis/rhabdomyolysis, and hypersensitivity reactions to the venom. Thrombotic microangiopathy may be another mechanism [35]. Therapeutic approaches for AKI after a wasp sting include correction of hypovolemia and improvement of renal ischemia, enhancement of toxic substance clearance from the circulation, and alleviation of direct adverse consequences caused by venom toxins, electrolyte imbalance, and heme proteins [36]. In this case, the patient was transferred to the ICU. Primary interventions include plasmapheresis and CRRT, which may be favorable for renal recovery.

ARDS, acute ischemic stroke, and AKI are possible complications of multiple wasp stings. However, there are no clear guidelines for the management of these complications. Further studies are required to explore the mechanisms underlying wasp stings.

Conclusions

Following a wasp sting, the patient’s clinical presentation can progress from localized reactions to severe systemic complications, including rare occurrences of cerebral infarction, ARDS, and AKI. However, this report has several limitations, including the lack of a systematic screening for thrombophilic tendencies, cervical vascular Doppler ultrasonography, and dynamic monitoring of creatine kinase (CK) levels to confirm rhabdomyolysis. Although there is a significant temporal association between the occurrence of complications and the sting event, other potential unknown factors cannot be entirely ruled out. It is recommended that clinicians maintain a high level of vigilance for multi-organ complications following a wasp sting and initiate early organ function assessment and supportive treatment. Future studies with larger sample sizes are necessary to further establish the causal relationship and underlying molecular mechanisms.