Black widow spider (Latrodectus renivulatus) envenomation in children in Saudi Arabia: a case series

Abstract Black widow spider (Latrodectus renivulatus) envenomation is a toxicological emergency affecting Middle Eastern countries. Young children may experience greater morbidity due to their small size relative to the amount of venom delivered. We describe four pediatric cases of severe black widow spider envenomation in Saudi Arabia. The neurological effects predominated, and all patients needed morphine for pain relief. All patients required admission to the pediatric intensive care unit (PICU). The durations of PICU stay and total hospital stay were 1–3 days and 2–5 days, respectively. Although Latrodectus antivenom is safe and effective, Latrodectus antivenom was unavailable, and no patients received antivenom. We believe that Latrodectus antivenom would rapidly relieve symptoms and shorten hospital stays.


Introduction
There are over 30 species of black widow spider (BWS) (Latrodectus) worldwide [1].In Saudi Arabia, there are two reported species; Latrodectus geometricus and Latrodectus renivulatus [2,3].The venom of Latrodectus spp.contains neurotoxic alpha-latrotoxin that interacts with nerve terminals and causes neurotransmitters release [4].The clinical syndrome of a BWS envenomation is latrodectism.The severity of BWS envenomation likely depends on the amount of venom delivered, the species of Latrodectus, and the age of the victim [5].In pediatric patients, the severity of BWS envenomation ranges from self-limiting symptoms to death [5][6][7][8][9].There are no reports focused on the pediatric age group in the Middle East.We describe four cases of BWS (Latrodectus renivulatus) envenomation in pediatric patients at tertiary care institutions in Saudi Arabia.

Case 1
A healthy 3-year-old boy, weighing 13.9 kg, felt the sensation of a "bite" on his left ear.He immediately felt pain at the site of the bite and had redness and swelling of the affected ear.The child was bitten around 8:00 PM, but his family did not take him to the emergency department (ED) until the next morning.The child's mother brought the spider suspected of biting the child, and the emergency physician identified it as a BWS.On ED arrival, he was irritable, crying, and complaining of severe left ear pain.He received hydrocortisone (30 mg) intravenously, his symptoms improved, and he was taken home.One day later, his parents brought him back to the ED with symptoms of tremor, skin eruption, weakness in the lower limbs with change in his gait, reduced oral intake, urinary retention, and lethargy.
His initial vital signs included: BP, 116/66 mmHg; HR, 146 beats/min; RR, 20 breaths/min; and temperature, 37.4 °C.Head, ears, eyes, nose, and throat examination showed mild redness of the left ear and moderately dry mucous membranes.Chest and abdominal examination revealed diffuse erythematous rash.Neurologically, the patient was alert and oriented, but irritable and crying persistently and inconsolably.He had a coarse tremor and showed weakness in all four limbs, associated with lower limb hyporeflexia.
In the PICU, he received an IV bolus of 0.9% saline (10 mL/kg), IV hydrocortisone (30 mg), paracetamol (200 mg), and morphine (1.3 mg).The patient was transferred to the general ward and received IV morphine, 1.3 mg every 4 h, IV hydralazine 1.3 mg every 4 h and IV maintenance fluids (dextrose 5% and 0.45% saline).An echocardiogram revealed normal heart anatomy and function.No further interventions were required.The patient recovered fully and was discharged four days after BWS envenomation.

Case 2
A healthy 1.5-year-old boy, weighing 10 kg, with no past medical history, presented to a community ED with right shoulder pain and the inability to walk after a spider bite.The mother reported that he was lying down when he screamed, became unable to stand, and vomited twice.The child's aunt saw a black spider on his shirt and brought to the ED where it was identified as a BWS.The patient was transferred to a tertiary care hospital because the community hospital lacked an intensive care unit.Upon arrival at the tertiary care hospital (6 h after the bite), he was irritable and persistently crying.He had no seizure or loss of consciousness.
On admission, the patient's vital signs included: BP, 114/60 mmHg; HR, 145 beats/min; RR, 25 breaths/ min; and temperature, 37 °C.He was conscious but irritable and uncomfortable.He had a delayed capillary refill time (3 s).Findings of local and systemic examinations were normal.
His venous blood gas showed mild metabolic acidosis, with pH 7.28, HCO 3 17 mmol/L, and PCO 2 of 35 mmHg.His initial creatine phosphokinase (CPK) was 260 U/L, which increased to 620 U/L on the second day before decreasing to 155 U/L on the third day.Other laboratory results were within normal limits.
He received a bolus of 0.9% saline (100 mL).The child was kept at NPO, and IV maintenance fluids were administered (60 mL/h of 5% dextrose and 0.9% saline).He vomited persistently for two days and received ondansetron (1 mg) as needed and electrolyte replacement.He received morphine infusion (10 mcg/ kg/h) for pain.After 24 h of morphine infusion, the pain resolved, and the patient did not need further analgesia.
An echocardiogram was normal except for an incidental finding of mitral regurgitation,.Electrocardiogram (ECG) results and cardiac enzyme activities were normal.On the third day after the BWS bite, he was transferred from the PICU to the general ward.He was discharged on the fourth day after the BWS bite.

Case 3
A healthy 2.9-year-old girl with up-to-date vaccinations and no allergies suddenly became agitated with nausea and intense pain in her right foot.Her brother noticed a black spider inside her right shoe and photographed it with his mobile phone (Figure 1).He immediately took his sister to a community ED, where she received a dose of morphine before transfer to a tertiary care hospital with a PICU.Upon arrival at the ED of the tertiary care hospital, the child was lethargic, and her right foot was mildly swollen.
Laboratory investigations revealed a slightly elevated CPK activity of 364 U/L, which decreased to 242 U/L the next day.Results of other laboratory investigations were within normal ranges.
She was admitted to the PICU and received IV morphine 1.5 mg every 4 h for the first 24 h.On the second day, her pain diminished, and she required only one dose of morphine.She received IV hydralazine 1.5 mg every 6 h for hypertension and oral diphenhydramine 15 mg every 6 h as a treatment for local itching and swelling.On the fourth day after the BWS bite, she had fully recovered and was discharged with oral co-amoxiclav 150 mg three times a day for five days.

Case 4
A 5.7-year-old girl weighing 18 kg presented to a community hospital after a spider bite.The girl and her brother saw the spider on the dorsum of her right foot.Her parents killed the spider and brought it to the hospital (Figure 2).Upon arrival at the community hospital, the patient was drowsy.During admission, her clinical condition worsened, and she showed agitation, declining level of consciousness, and abnormal movements.Eight hours after the BWS bite, her family signed for discharge against medical advice and took the patient to a tertiary care hospital.Upon arrival at the tertiary hospital ED, she had abnormal movements, hallucinations, drowsiness, and intense pain in the dorsum of the right foot.
Her vital signs included: temperature, 39.0 °C; HR, 110 beats/min; RR, 28 breaths/min; and oxygen saturation, 97% in room air.She was extremely irritable and showed tremors in her extremities (predominantly the upper extremities), with no clonus or rigidity.Abdominal examination revealed that her abdomen was moderately tender, without rigidity.The remainder of her examinations was normal.Initial laboratory investigations showed leukocytosis with a white blood cell count of 16.3 × 10 9/ L and platelet count of 489 × 10 9/ L. Results of other laboratory and imaging investigations were normal.
After 6 h of initial resuscitation and pain management, the patient was admitted to the PICU.She was alert and conscious but still irritable with photophobia and periods of visual and auditory hallucinations.Cranial nerves were intact.She had tremors in her upper and lower limbs, with mild hypotonia, brisk reflexes, and grade 4 muscle power.Her pain was 8/10 and not relieved by paracetamol.She received morphine and midazolam, which alleviated her pain and allowed her to sleep.Her cardiopulmonary examination was normal, apart from persistent hypertension treated with IV hydralazine 1.8 mg every 4 h.Abdominal examination revealed generalized tenderness with guarding, which improved with morphine.She had mild redness at the site of the bite.
While in the PICU, she received IV co-amoxiclav 15 mg/kg every 8 h, hydralazine 1.8 m every 4 h, IV morphine 1.4 mg every 4 h as needed, and midazolam 0.7 mg every 4 h as needed.She was transferred to the general ward two days after the bite.Her pain, tremor, abdominal guarding, and hypertension improved gradually over the next four days.She recovered fully and was discharged after five days of hospitalization.

Discussion
The onset of symptoms occurred promptly after the bite in all four cases.Spider identification occurred by direct examination of spider or through photography.All patients showed grade III severity based on muscular pain combined with autonomic disturbances [5].Neurological symptoms were predominant and included lethargy, weakness, tremor, ataxia, hyporeflexia, and hypotonia.All patients had severe pain, restlessness, and inconsolability (Table 1).All patients received morphine for pain.All patients had autonomic manifestations with tachycardia and/or hypertension, and three of four patients required hydralazine.In Case 1, premature discharge led to revisit when the patient developed more severe symptoms of dehydration, metabolic acidosis, tremor, and urinary retention.Two patients had mild CPK elevations that improved with hydration.Other symptoms included fever, abdominal pain with guarding, nausea, vomiting, dehydration, metabolic acidosis, and rash.All patients were admitted to the PICU for monitoring.The durations of PICU stay and total hospital stay were 1-3 days and 2-5 days, respectively.None of the patients received Latrodectus antivenom because it was not available.Unlike a previous report of BWS bite in pediatrics, in which all patients with severe symptoms received benzodiazepines [5], only one patient received midazolam in our case series.
A BWS bite is a toxicological emergency in Saudi Arabia.Thus far, there have been two published case series of BWS envenomation from the southern regions of Saudi Arabia (Asir and Al Baha) [8,9].In both reports, the patients were older (teenagers or adults).Clinical presentations included a board-like rigid abdomen, pulmonary edema, angioedema, ptosis, rhabdomyolysis, and acute kidney injury.None of our patients had these findings.Latrodectus antivenom was effective in reversing grade III envenomation in four patients from Al Baha [8].
Glatstein et al. reported 93 cases of pediatric BWS envenomation.Common symptoms included irritability, muscle cramps, and autonomic disturbances (diaphoresis, tachycardia, and hypertension) [5].These symptoms were consistent with those of our patients.Approximately 15% of patients received L. mactans antivenom, which was associated with rapid improvement of symptoms within a few hours.The patients who received the antivenom did not need further analgesia and had shorter stays in the ED, with minor adverse effects.No patient in that series received hydralazine.In contrast, time to full recovery in our cases was 2-5 days without antivenom.
BWS antivenom is effective.Clark et al. found that antivenom produced symptom improvement after a mean of 31 min [10].Monte et al. found that patients with moderate and major symptoms had a shorter duration of symptoms, but patients with minor symptoms did not [11].In pediatric BWS envenomation, antivenom was associated with a shorter duration of hospital stay, rapid improvement of symptoms, and lower administered dosages of analgesia, with no significant adverse effects [5].In a report from the region of Al Baha, four out of nine patients received antivenom, which appeared effective up to 30 h from the bite [8].Lastly, Dart et al. in the US conducted a phase III multi-center, randomized, double-blind, placebo-controlled trial of new equine derived F(ab′) 2 antibody fragments.The new purified F(ab′) 2 antivenom reduced treatment failures and improved the pain intensity [15].
Limitations of this case series include the retrospective chart review design, which may miss some data.Also, the data were collected from two PICUs in the same region may reflect more severe envenomation.This case series may not represent the entire spectrum of BWS envenomation presentations.

Conclusion
Neurological symptoms, pain, and hypertension were the predominant features of BWS envenomation in our four pediatric patients.Symptomatic treatment with morphine, paracetamol, and hydralazine was the cornerstone of conservative management.All of our cases of BWS envenomation were severe enough to warrant PICU admission.The duration of the PICU stay ranged from 1 to 3 days.The unavailability of BWS antivenom likely prolonged PICU and hospital stays.Also, the medical teams used different regimens to manage the patients and there were no standard supportive guidelines.Developing standard treatment guidelines and making Latrodectus antivenom available may improve outcomes and shorten hospital stays.

Figure 1 .
Figure 1.case 3: The photograph of a redback spider captured by the patient's brother.The patient was bitten on the right foot.

Figure 2 .
Figure 2. case 4: spider with red ventral pattern that was killed by patient's parents.The patient was bitten on her right foot.

Table 1 .
Patients' characteristics and management.