Epidemiological and clinical characteristics of scorpionism in Shiraz (2012-2016); development of a clinical severity grading for Iranian scorpion envenomation.

Background: Scorpionism is a public health problem in some provinces in Iran. The present study aimed to assess the clinical manifestations of scorpion envenomation in Shiraz and determine a clinical severity grading for Iranian scorpion envenomation in order to suggest a treatment guideline for emergency physicians.
Methods: In this analytic retrospective study, all medical charts of patients with scorpion sting admitted in the adult medical toxicology center in Shiraz during July 2012 to July 2016 were assessed. Data regarding the patient's age, gender, sting site, month of envenomation, time of sting, clinical manifestations, vital signs, presence of blood or hemoglobin in urine analysis, duration of admission, color of scorpion, received treatments, and administration of scorpion antivenin were recorded.
Results: The scorpions in Shiraz and its suburban area were classified into two groups: yellow scorpions ( Mesobuthus eupeus, Mesobuthus caucasicus , and Compsobuthus matthiesseni) and Hottentotta scorpions (Hottentotta jayakari and Hottentotta zagrosensis). A total of 126 cases of scorpion stings were assessed. About 59% (n=74) were males. The patients aged 8-63 years (mean age, 33.8±11.5 years). About 38.4% (n=48) of the stings occurred during summer. More than 40% of patients (n=51) referred to the emergency department (ED) at night. Localized pain was the most frequent presenting complaint (76.2%). The most frequent general symptom was nausea (6.3%). The most prevalent envenomation site was the lower extremities followed by upper extremities (43.5% and 41.9%, respectively). Based on the clinical severity grading for Iranian scorpion envenomation, 65, 43, and 18 patients (51.6%, 34.1%, and 14.3%) were classified in the grades I, II, and III, respectively. Eighty-one (73%) patients stayed in the ED from 1 to 6 hours, and 30 (27%) patients stayed for >6 hours for observation. Severe localized pain was more prevalent in stings with Hottentotta scorpions than yellow scorpions (P=0.01). The season of envenomation with Hottentotta scorpions was summer in all cases, but envenomation with yellow scorpions was seen throughout the year. All patients received symptomatic treatment, and five were given scorpion antivenin. No death was reported.
Conclusion: Hottentotta jayakari is recommended to be listed among the medically important scorpions in Iran. Moreover, scorpion-stung patients in geographical regions where Hemiscorpius lepturus and Androctonus crassicauda are not prevalent may be treated in outpatient departments. The presented grading system can be used for treating patients with scorpion envenomation.

↑ What is “already known” in this topic:

In Iran, about 51 scorpion species have been reported, among which 11 species are medically important. There is still no grading system for the severity of Iranian scorpion envenomation and no clear treatment guidelines for emergency physicians.

→ What this article adds:

Hottentotta jayakari species should be regarded among the medically important scorpions of Iran. For the first time, a clinical severity grading for Iranian scorpion envenomation was presented.

Introduction

Scorpions have been living on earth for more than 400 years (1). So far, about 2000 scorpion species have been identified, 25 of which have medical significance (2,3). Their venom differs among different species and consists of proteins and other substances (4). Annually, about half a million people are stung by scorpions worldwide with a mortality rate of 3250 individuals (5,6). Scorpion stings are one of the most important environmental health hazards in Iran. Although, more than fifty thousands of scorpion stings are reported annually, around 75% of fatal cases are reported from Khuzestan, Sistan-Baluchestan, Kerman and Hormozgan provinces (7-9).

The Hemiscorpius lepturus and Androctonus crassicauda species are responsible for most fatal envenomation cases in Iran (9-12). The clinical manifestations of scorpion envenomation can be a challenge for emergency physicians since they are diverse, ranging from mild burning sensations at the sting site to critical fatal conditions (13).

In Iran, about 51 scorpion species have been reported, among which 11 species are medically important (9,14). The characteristics of these medically important scorpions and their clinical envenomation manifestations are provided in Table 1 (9-12,14-33). Previous studies have reported the clinical manifestations of scorpion stings in provinces with high rates of scorpionism (7,31-89). However, there is still no grading system for the severity of Iranian scorpion envenomation and no clear treatment guidelines for emergency physicians. Moreover, there is only one study on scorpion envenomation in Shiraz, reporting patients with scorpion envenomation to a tertiary hospital from southern Iran (90).

Table 1

Medically important scorpions of Iran and clinical manifestations of their stings (9-12,14-33)

Scorpion species	Apparent color	Size	Clinical manifestations of the sting
Hemiscorpius lepturus	Yellow	Male: 5cmFemale: 7.5-8cm	Local: minor to mild local pain, local pruritus, erythema, inflammation, ecchymosis, severe swelling, blisters, cellulitis, extensive skin necrosis at the site of the sting. Systemic: drowsiness, fatigue, irritability, restlessness, hyperthermia, pallor, sweating, hypotension, cool extremities, tachycardia, muscle spasms, convulsion. Laboratory: leukocytosis, hematuria, hemoglobinuria, myoglobinuria (rhabdomyolysis), proteinuria, hemolytic anemia, elevated liver enzymes, increased PT and PTT, DIC, HUS, acute renal failure
Androctonus crassicauda	Black	11-12cm	Local: local burning pain at the site of the sting. Systemic: due to the increased release of acetylcholine and catecholamines: drowsiness, irritability, restlessness, decreased level of the consciousness, miosis, tachypnea, excessive sweating, salivation, diarrhea, nausea, vomiting, urination, severe abdominal cramps, numbness of limbs, tachycardia, filiform pulse, hypotension, hypothermia, cool extremities, decreased tendon reflexes, cyanosis, excessive thirst, ECG changes, acute pulmonary edema, melena, bloody vomiting. Laboratory: leukocytosis, granulocytosis, lymphopenia, glucosuria, hemoglobinuria, proteinuria
Buthotus (Hottentotta) saulcyi	Yellow	12-13 cm	Severe pain at the site of the sting, other clinical manifestations (are questionable)
Odontobuthus doriae	Yellow	7-8.5 cm	Prolonged severe pain at the site of sting with radiation to its periphery, severe muscle contractions in the affected extremity (twitching), irritability, restlessness, tachycardia, tachypnea, dyspnea, unilateral acute pulmonary edema
Mesobuthus eupeus	Yellow	5-6 cm	Local: moderate to severe pain or burning sensation at the site of sting, Systemic: thirst, dry mouth, headache, nausea, irritability, restlessness, tachycardia, tachypnea, transient ophthalmoplegia
Orthochirus scrobiculosus	Black	2.5-4 cm	Severe pain and prolonged itching at the site of sting, one death has been reported
Apistobuthus pterygocercus	Yellow	7-8 cm	Anxiety, miosis, rhinorrhea, dacryorrhea, hypersalivation, tachypnea, shortness of breath, wheezing, gastric distention, and abdominal bulge
Mesobuthus (Olivierus) caucasicus	Yellow	6-6.5 cm	Similar to the Mesobuthus eupeus
Hemiscorpius acanthocercus	Yellow	Male: 5cmFemale: 7.5-8cm	Similar to the Hemiscorpius lepturus, one death has been reported
Hottentotta zagrosensis (previously named as Buthotus schach)	Black	13 cm	Not reported
Compsobuthus matthiesseni	Yellow	4-5 cm	Hematuria (is questionable)

DIC: disseminated intravascular coagulation; ECG: electrocardiographic; HUS: hemolytic uremic syndrome; PT: prothrombin time; PTT: partial prothrombin time

The current study aimed to assess the clinical manifestations of scorpion envenomation in Shiraz and to determine a grading system regarding its severity via reviewing its clinical manifestations in Iran to provide a treatment guideline for emergency physicians.

Methods

Shiraz (N 52°32′E′37°29), the capital of Fars province, is the sixth most populated city in Iran situated in the southwest of the country and has a mild climate. Its population was about 1,500,000 in the 2011 census (91). In July 2012, the Division of Medical Toxicology was established in the Emergency Room of Hazrat Ali-Asghar (p) Hospital, as the only adult medical toxicology center in Shiraz. Until then, there was no information on the most common scorpion species and clinical manifestations of their stings in this geographical region. Hence, scorpions, brought by afflicted patients, were kept in alcohol 70% and sent to the laboratory of the Department of Environmental Health of Kashan University of Medical Sciences. These scorpions were identified based on the diagnostic keys for Iranian scorpions (92-94). In this analytic retrospective study, all medical charts of patients with scorpion sting admitted during July 2012 to July 2016 were assessed. Data regarding the patient's age, gender, site of sting, month of envenomation, time of sting, clinical manifestations, vital signs, presence of blood or hemoglobin in urine analysis (U/A), duration of admission, color of scorpion, received treatments, and administration of scorpion antivenin were extracted and recorded. If the color of the scorpion was not in the records, the patients or their families were called. Stings occurring in regions other than Shiraz and its suburban area were excluded from the study. Also, patients with underlying cardiovascular and renal diseases and those who were receiving anticoagulants were excluded. Scorpions of the genus Hottentotta differ in terms of size and color with other solid yellow scorpions (94). In fact, stings with these great size scorpions with different coloration are more intimidating. Moreover, as they belong to a relatively large species of scorpions, severe clinical symptoms would be expected on their stings, depends upon the large amount of the venom injected. Therefore, the scorpion stings were divided into stings from Hottentotta and yellow scorpions. A classification was developed on the basis of the reported clinical manifestations of scorpion-stung patients from Iran (9-12,14-33) and was utilized to grade the clinical severity of scorpion envenomation for the stung patients.

Data were analyzed by using SPSS software, version 22.0 using Mann-Whitney U, Fisher's exact, Pearson's Chi-square, and student's t-test. A p-value of less than 0.05 was considered statistically significant.

Ethical considerations

The study was approved on May 23, 2016 by the Committee of Ethics in Research, Medical School, Shiraz University of Medical Sciences and registered as IR.SUMS. MED.REC.1395.S98.

Results

A total of 28 scorpion samples of the patients were collected. After identification at the laboratory, the scorpions in Shiraz and its suburban area were classified into two groups: yellow scorpions (Mesobuthus eupeus (n=10), Mesobuthus caucasicus (n=9), and Compsobuthus matthiesseni (n=2)) and Hottentotta scorpions (Hottentotta jayakari (n=6) and Hottentotta zagrosensis (1)) with respective prevalence (Fig. 1 to 5).

Fig. 1

Fig. 5

Mesobuthus eupeus (original picture)

Mesobuthus caucasicus (original picture)

Compsobuthus matthiesseni (original picture)

Hottentotta jayakari (original picture)

Hottentotta zagrosensis, previously named as Buthotus schach (dead specimen; original picture)

During the study period (July 2012 to July 2016), the total number of scorpion sting cases reviewed was 126. The gender distribution showed 59% (n= 74) males and 41% (n=52) females. The patients aged 8 to 63 years (mean age of 33.8±11.5 years). About 38.4% of the stings occurred during summer, most of which occurring in August. More than 40% of patients (n=51) referred to the emergency department (ED) at night between 00.00 am to 06.00 am.

The most prevalent site of envenomation was the lower extremities (53 cases, 43.1%), followed by upper extremities (52 cases, 42.3%), trunk (10 cases, 8.1%), and head and neck (9 cases, 7.3%). Also, there was one case of simultaneous hand and foot sting and one case of simultaneous trunk and hand sting.

The vast majority of the patients (95; 75.4%) had only localized manifestations including local mild to severe pain (n=81; 64.3%), burning sensation (n=39; 30.1%), mild erythema (n=32; 25.4%), mild swelling (n=12; 9.5%), pruritus (n=8; 6.3%), and tenderness (n=2; 1.6%). The general symptoms included nausea (n=8; 6.3%), vertigo (n=4; 3.2%), fatigue (n=3; 2.4%), dyspnea (n=3; 2.4%), sweating (n=1; 0.8%), shivering (n=1; 0.8%), chest pain (n=1; 0.8%), flushing (n=1; 0.8%), and epigastric pain (n=1; 0.8%) with no systemic involvement. Also, 80 (63.5%) and 15 (11.9%) cases were diagnosed as yellow and Hottentotta scorpion stings, respectively. In 31 (24.6%) of the stung patients, the color of the scorpions was not determined.

The clinical manifestations of scorpion stings with respect to the scorpions’ color and size are given in Table 3. Severe localized pain was more prevalent in stings with Hottentotta than yellow scorpions (p=0.01, Fisher's exact test). In addition, the patients stung with Hottentotta scorpions needed more antivenin (p=0.002, Fisher's exact test). There were no significant statistical differences between these two groups regarding other clinical manifestations, vital signs, clinical severity grading, or length of ED stay.

Table 3

Comparison of clinical manifestations of scorpion stings with respect to the scorpions’ color and size

Clinical manifestations	Yellow scorpions(no=80)	Hottentotta scorpions(no=15)	P value
Local pain	37 (46.3%)	4 (26.7%)	0.130
Burning sensation	34 (42.5%)	3 (20%)	0.085
Mild erythema	26 (32.5%)	4 (26.7%)	0.454
Severe local pain (with or without radiation to its periphery)	20 (25%)	9 (60%)	0.010
Mild swelling	10 (12.5%)	2 (13.3%)	0.602
Local pruritus	6 (7.5%)	1 (6.7%)	0.695
Local paresthesia	1 (1.3%)	0 (0%)	0.842
Nausea	5 (6.3%)	0 (0%)	0.415
Fatigue	2 (2.5%)	1 (6.7%)	0.406
Dyspnea	1 (1.3%)	0 (0%)	0.842
Vertigo	2 (2.5%)	1 (6.7%)	0.406
Sweating	1 (1.3%)	0 (0)	0.842
Shivering	0 (0%)	1 (6.7%)	0.158
Chest pain	1 (1.3%)	0 (0%)	0.842
Flushing	1 (1.3%)	0 (0%)	0.842
Epigastric pain	1 (1.3%)	0 (0%)	0.842
Muscle spasm	1 (1.3%)	0 (0%)	0.842
Pulse rate/min (mean ±SD)	82.50±12.81	86.57±10.88	0.828
Respiratory rate/min (mean ±SD)	18.06±2.20	17.42±2.06	0.792
Systolic blood pressure (mmHg) (mean ±SD)	117.01±16.02	127.21±16.42	0.791
Diastolic blood pressure (mmHg) (mean ±SD)	76.00±14.60	80.42±10.72	0.297
Microscopic hematuria	9 (11.3%)	0 (0%)	0.197
Severity grade I	42 (52.5%)	6 (40%)	0.272
Severity grade II	27 (33.8%)	8 (53.3%)	0.126
Severity grade III	11 (13.8%)	1 (6.7%)	0.398
Length of ED stay (˂6h)	51 (71.8%)	9 (60%)	0.270
Scorpion antivenin administrated	1 (1.3%)	4 (26.7%)	0.002

SD: standard deviation; ED: emergency department

The classification shown in Table 2 was utilized to grade the clinical severity of scorpion envenomation for all cases. According to the present clinical severity grading classification, 65, 43, and 18 of the patients (51.6%, 34.1%, and 14.3%) were classified in the grades I, II, and III, respectively.

Table 2

Grades of scorpion sting severity on the basis of the reported clinical manifestations of scorpion-stung patients from Iran (9-12,14-33)

Grade	Clinical picture
I	• Mild localized symptoms‏
II	• Moderate to severe local pain‏ • or microscopic hematuria
III	• Prolonged severe pain at the site of sting with radiation to its periphery (not responding to treatment‏),• and/or prolonged local severe itching (not responding to treatment‏),• and/or general symptoms‏ • or microscopic hemoglobinuria (in endemic regions for H. lepturus or H. acanthocercus‏)
IV	• Severe cutaneous manifestations (in endemic regions for H. lepturus or H. acanthocercus‏) • and/or abnormal vital signs• and/or muscle spasm, twitching‏ • and/or dark red urine (gross hemoglobinuria‏)• and/or systemic involvement: cardiovascular and/or respiratory and/or neurological disorders and/or acute renal failure‏ • and/or hemolysis, and/or DIC, and/or HUS

DIC: disseminated intravascular coagulation; HUS: hemolytic uremic syndrome

In all cases, the season of envenomation with Hottentotta scorpions was summer, but envenomation with yellow scorpions was reported throughout the year.

The length of ED stay was classified into two groups: 81 (73 %) patients (of 111 patients with valid data) stayed from 1 to 6 hours, and 30 (27%) patients stayed for >6 hours for observation. Thirty-two patients (25%) discharged themselves against medical advice.

In general, all patients received intravenous hydrocortisone and intramuscular antihistamines injections. Some of the patients received local injection of lidocaine, analgesics, meperidine (pethidine), and/or local application of ice pack to the sting site for pain relief, and five (4%) patients received scorpion antivenin. Scorpion antivenin was given to the patients with grade III clinical severity grading classification.

In 12 cases (2 males and 10 females) of envenomation with yellow scorpions, microscopic hematuria was reported in the U/A (positive hemoglobin/blood in urine dipstick together with microscopic red blood cells). All patients were discharged in good condition. There was no death.

Discussion

Most fatal scorpion envenomations in Iran are related to H. lepturus and A. crassicauda species (9-12). This study found no envenomation case with these species in Shiraz and its suburbs. Azizi et al. in 1998 studied scorpions in the villages around Shiraz and reported that M. eupeus, A. crassicauda, and H. lepturus fauna were respectively more prevalent (95). Moreover, other researchers have recently reported M. eupeus, A. crassicauda, and Orthochirus scrobiculosus fauna in villages around Shiraz (96). The reason for the different fauna reported in these two studies and the species of the scorpion samples in the current study is unknown, but it might be attributed to the reduced population of some species due to the modernization of rural areas around Shiraz.

The clinical manifestations of stings by medically important scorpions in Iran have been previously reported except for H. schach and C. matthiesseni. In addition, the systemic clinical manifestations of envenomation by M. eupeus and H. saulcyi are questionable. Regarding the clinical manifestations of sting by M. eupeus, Radmanesh believes that the systemic manifestations of sting by this scorpion are caused by the fear of being stung, and this species does not cause severe clinical manifestations (9,15). However, transient ophthalmoplegia following envenomation by M. eupeus has been reported from Iran (31).

The only study reporting the clinical manifestations of envenomation with M. eupeus in other countries is a retrospective study by Ozkan and Kat on 152 patients in the Sanliurfa region of Turkey (97). The most prevalent local clinical manifestations of M. eupeus were swelling, hyperemia, pain, burning, itching, and numbness, and systemic clinical manifestations were reported in 9% of the cases. Systemic manifestations consisted of dry mouth, thirst, sweating, hypotension, nausea, hypertension, difficulty in breathing, tachycardia, an increase of bronchial secretion, and cyanosis with respective prevalence. However, laboratory identification of the species was not done, and the species were identified according to the color of the scorpion self-reported by the patients (97). Therefore, other species might have been responsible for the so-called local and systemic manifestations.

It has been reported that the clinical manifestations of envenomation with M. caucasicus is similar to those of M. eupeus (9,72,73). In the present study, the most common general symptoms caused by envenomation with yellow scorpions were as follows: nausea (n=8; 6.3%), vertigo (n=4; 3.2%), fatigue (n=3; 2.4%), dyspnea (n=3; 2.4%), sweating (n=1; 0.8%), shivering (n=1; 0.8%), chest pain (n=1; 0.8%), flushing (n=1; 0.8%), and epigastric pain (n=1; 0.8%).

However, in contrast to Ozkan and Kat’s study (97), the vital signs were in the normal limit upon presentation and during admission. Most patients had localized manifestations, and no systemic involvement was found. However, in 12 (10%) cases of envenomation with yellow scorpions, microscopic hematuria was reported. Menstruation might have been responsible for hematuria since 10 patients were female, and this was not recorded in the hospital records. Moreover, hematuria was reported in evenomations by C. matthiesseni species (9,92).

This is the first report regarding scorpion envenomation in adults, form Shiraz and its suburbs, Iran. The only related study on scorpionism in Shiraz was done by Sagheb et al. who had assessed referred patients with scorpion envenomation to a tertiary hospital from southern Iran (90). They found that 6% of the patients had systemic clinical manifestations, among which acute renal failure and disseminated intravascular coagulation were the most common. H. lepturus was responsible for these two systemic manifestations. The current study is not comparable with this study since all referrals including children from southern Iran, and other provinces were involved.

It is for the first time in Iran that envenomations by H. jayakari species are reported. Since this species has been found in other parts of Iran (11,83,94,98-101), it may be listed among the medically important scorpions of Iran. It is hunted in Sistan-Baluchestan (83), Hormozgan (94,100), and Fars (11) provinces and Qeshm (101), Kish (99), Hengam, and Tonb-e Bozorg (98) islands of the Persian Gulf.

The clinical manifestations of H. zagrosensis sting (previously named as Buthotus schach) (9,11,18,40,44,92,93,102-104) not previously reported from Iran. A percentage of stings by Hottentotta scorpions were caused by this species. Hottentotta zagrosensis is hunted in Fars, Khuzestan, West Azarbaijan (11,40,44,96,105-107), Lorestan (108), Qazvin (109), Chaharmahal-Bakhtiari (110,111), and Kohgiluyeh-Boyer-Ahmad (112) provinces in Iran.

It was found that scorpion envenomations are more common in summer and at night, in line with other studies on scorpion envenomation (7,28,40-52,65,66,69,70,74-83,87-89). Moreover, envenomations with Hottentotta scorpions were only reported in summer, and the pain was more prevalent in patients stung by Hottentotta scorpions compared to yellow scorpions. This could be attributed to the bigger size of telson of Hottentotta scorpions. According to the present study, despite the large size, the severity of clinical manifestations of Hottentotta species envenomation is similar to other studied yellow scorpions, except for severe localized pain.

About 70% of the patients were admitted for 1-6 hours, and some insisted on being discharged despite medical advice to stay longer, representing their good general condition. Since the severity of most envenomations was grade I and II, it seems that scorpion stung patients in Shiraz and other geographical regions in Iran, where H. lepturus and A. crassicauda stings are not prevalent, can be treated in the outpatient departments, not highly crowded emergency departments.

In this study, a grading system for the severity of scorpion envenomation was presented for the first time based on the clinical manifestations of scorpion stings in Iran. This grading could be used for treating patients. So, those with grades I and II could be treated symptomatically, and scorpion antivenin could be used for patients with grades III and VI, similar to the protocol used in managing the patients. However, no patient with grade VI severity was reported.

In Iran, Razi Vaccine and Serum Research Institute is responsible for producing anti-scorpion serum. This polyvalent scorpion antivenin is prepared from the purified plasma of healthy horses immunized with venoms of the six medically important scorpion species in Iran including O. doriae, M. eupeus, A. crassicauda, B. saulcyi, B. schach, and H. lepturus (113). As previously mentioned, H. lepturus and A. crassicauda are among the most dangerous scorpion species in Iran, and their stings can be fatal (9-12). Although there is no definite treatment protocol for envenomation by these species, Valavi (114) suggests that the best treatment for such stings, in cases presenting no systemic or general symptoms, is slow intravenous administration of one ampule of scorpion antivenin after cutaneous testing. Then, the decision to administer more antivenin should be made according to repeated urine tests (appearance of hemoglobinuria) in cases of H. lepturus envenomation and the manifestation of other signs and symptoms of A. crassicauda sting. However, in patients with hemoglobinuria or systemic or general symptoms, 3-6 intravenous antivenins should be slowly prescribed after cutaneous testing depending on the severity of symptoms. If the species of scorpion is not known, patients should be treated considering the progression of signs and symptoms, appearance of hemoglobinuria, or other systemic manifestations (114).

In this study, only the adult patients admitted to medical toxicology center in Shiraz were assessed. Patients treated in outpatient departments or not referring to hospitals for treatment due to the mild symptoms were not included. In other words, scorpion envenomation is definitely more prevalent in Shiraz compared with the current statistics. Also, the results cannot be generalized to children since only the adults were included. Furthermore, like any other retrospective studies, they were other limitations in our study. Some of the data were missing in some of the patients’ chart. Also, some of the charts were missing and thus we could not include them in the study.

Conclusion

It is recommended to list H. jayakari among the medically important scorpions of Iran. Moreover, it seems that patients stung by scorpions in geographical regions in which H. lepturus and A. crassicauda stings are not prevalent could be treated in outpatient departments. The presented grading system can be used for treating patients with scorpion envenomation. The stung patients with grades I and II envenomation could be treated symptomatically, and scorpion antivenin could be used only for patients with grades III and VI.

Acknowledgment

The authors would like to thank the nurses of the Emergency Room, the Division of Medical Toxicology, Hazrat Ali-Asghar (p) Hospital, Shiraz, Iran for their assistance in collecting the scorpion samples of the patients.

Conflict of Interests:

The authors of this article declare that they have no competing interests.