Document Type: Original Article

Authors

Addiction Research Centre (ADRC), Mashhad University of Medical Sciences, School of Medicine, Mashhad, Iran

Abstract

Background: In order to describe the patients and evaluate the effectiveness of treatments for widow spider envenomation, investigators require a reliable assessment tool. In this paper, the development of a clinical index for measuring the widow spider bite severity, Latrodectus Envenomation Severity Score (LESS), is described.
Methods: According to the valid methods for index development, a Delphi group process was applied. A panel of 13 experienced medical toxicologists and physician experts in treatment of black widow spider bites was assembled in December 2013. The participants were asked to score clinical manifestations of Latrodectus envenomation based on their importance on the severity and patients’ prognosis. Hence, an initial draft of the severity index was developed and in the second phase of study, the draft was discussed in a focus group of experts to finally comment on each variable and vote about the final scores.
Results: The proposed version of LESS comprises of 34 clinical items categorized in 8 organ systems. The index includes definition of each clinical variable to help users of the index how to ascertain or rule out the clinical finding. The maximum theoretical score according to LESS is 87. Acute renal failure, myocarditis, pulmonary edema and ileus received the highest scores in this index.
Conclusion: The LESS is a new assessment tool that is designed to more objectively evaluate the severity and progression of envenomation in victims of widow spider bite. The prognostic-ability, reliability and sensitivity to change of the index should be investigated in future studies.
 
How to cite this article: Monzavi SM, Afshari R. Development of Latrodectus Envenomation Severity Score (LESS); a Severity Index for Widow Spider Bite: Initial Step. Asia Pac J Med Toxicol 2014;3:18-22.

Keywords

How to cite this article: Monzavi SM, Afshari R. Development of Latrodectus Envenomation Severity Score (LESS); a Severity Index for Widow Spider Bite: Initial Step. Asia Pac J Med Toxicol 2014;3:18-22.

Introduction

Venomous bites of Latrodectus genus or the widow spiders can produce several morbidities due to severe neurotoxicity caused by their venom. A widow spider bite induces effects ranging from puncture marks without apparent clinical signs to systemic envenomation syndrome known as “latrodectism” that classically includes generalized muscle pain, diaphoresis, cramps, vomiting and chills (1-3). Moreover, in serious cases, metabolic acidosis, electrolyte disturbances, hypertension, dysrhythmia, renal failure and ileus may occur (2-5).

Systemic Latrodectus envenomation develops in approximately a third of victims (2). In addition, all possible consequences may not occur in a victim due to individual’s characteristics, the amount of venom injected into blood circulation, variability in widow spider species and the impact of climate and season on the quality of venom (6). Clinical picture of systemic envenomation exhibits in a dynamic trend that initiates with limited localized pain progressing to system organ involvements (1,2). In this regard, severe venom effects may not become evident in the first 24 hours (7). On the other hand, the envenomation syndrome may start with critical signs in some patients, but fail to deteriorate in later stages. Hence, repeated assessment of the patient has been recommended for the efficient management. Furthermore, the protean nature of the disease complicates any evaluation and comparison of envenomation severity in similar studies. Although, there have been some efforts for grading the severity of Latrodectus envenomation (8), those scales are unable to quantitatively describe the exact condition and compare two patients with each other. In order to assess the effectiveness of treatments for widow spider envenomation, investigators have used various outcome measures including pain (using visual analogue scale) and sweating (using hyperhidrosis disease severity scale) (9-11). However, these features represent only a part of envenomation syndrome and do not reveal the clear overall condition.

In order to standardize the evaluation of severity of widow spider bites, a major concern has been raised in Mashhad Medical Toxicology Centre for development of a comprehensive instrument.  In this paper, the development of a clinical index for the measurement of widow spider bite severity, Latrodectus Envenomation Severity Score (LESS), is described.

Methods

According to the valid methods for index development (12), a Delphi group process was applied that provides an environment for a group of experts to express their opinions anonymously (12,13). A panel of 13 experienced medical toxicologists and physician experts in treatment of black widow spider bites in Khorasan region was assembled in December 2013. The purpose of the panel was to define and standardize a clinical index for assessment of widow spider bite severity. A questionnaire was given to participants that contained a comprehensive list of clinical features (symptoms, signs and laboratory findings) of widow spider bite reported in the literature and medical toxicology textbooks (1-9,14-16), amended with discussion with experts in the management of the disease. 

In order to score each clinical variable a general question was asked from the participants: Which of the following clinical presentations has the higher importance for giving the patient more serious or intensive care or rule out the discharge of the patient? The participants were asked to score each variable on a scale of 0 (no importance) to 5 (most important) to indicate the weight of each variable for measuring disease severity. The scores of each item were analyzed using Microsoft Excel software (Microsoft Corp., Redmond, WA, USA) and the results were showed with mean and standard deviation (SD), median and interquartile range (IQR), and mode.

Consequently, an initial draft of the severity index was developed. In the second phase of study, the draft was discussed in a focus group of experts to finally comment on each variable and vote about the final scores. Definition of each clinical variable was also provided to help users of the index how to ascertain or rule out the clinical finding.

Results

Development of the severity index

The results of the scores for clinical features of widow spider bite allocated by the panel members (in the Delphi process) are illustrated in the table 1. Based on these scores, the initial draft of the LESS was proposed and presented to the focus group. For most variables, the mean of allocated scores was considered to determine the score on the LESS.

Table 1. Scores allocated by the panel members (in the Delphi process) to the clinical features of widow spider bites based on their importance in envenomation severity

Clinical feature

Mean (SD)

Median (IQR)

Mode

Acute renal failure

4.8 (0.4)

5.0 (4.5-5.0)

5.0

Myocarditis

4.7 (0.9)

5.0 (4.0-5.0)

5.0

Pulmonary edema

4.6 (0.7)

5.0 (4.0-5.0)

5.0

Ileus

4.1 (1.2)

5.0 (3.0-5.0)

5.0

Dysrhythmia

3.8 (1.7)

5.0 (3.0-5.0)

5.0

Metabolic acidosis

3.5 (1.2)

4.0 (2.3-4.0)

4.0

Dehydration

3.2 (1.1)

3.0 (2.0-4.0)

4.0

Generalized muscle pain

3.2 (1.1)

3.0 (2.0-4.0)

2.0

Hyperkalemia

3.1 (1.4)

3.0 (2.0-4.0)

3.0

Chills / Muscle cramping

3.1 (1.3)

3.0 (2.5-4.0)

3.0

Abdominal rigidity

3.0 (1.6)

3.0 (1.0-2.0)

4.0

Diaphoresis

3.0 (1.4)

3.0 (2.0-4.0)

3.0

Bradycardia

3.0 (0.9)

3.0 (2.5-3.5)

3.0

Hypertension

2.8 (1.0)

3.0 (2.0-4.0)

3.0

Dyspnea

2.7 (1.2)

3.0 (1.5-4.0)

3.0

Dermal necrosis

2.7 (1.4)

3.0 (2.0-4.0)

2.0

Vomiting

2.7 (1.2)

3.0 (2.0-3.0)

2.0

Restlessness

2.6 (0.5)

3.0 (2.0-3.0)

3.0

Hypokalemia

2.5 (1.6)

3.0 (1.0-4.0)

3.0

Sinus tachycardia

2.4 (1.1)

2.0 (1.5-3.0)

2.0

Abdominal pain

2.3 (1.0)

2.0 (1.5-3.0)

2.0

Confusion / Hallucination

2.1 (1.1)

2.0 (1.5-3.0)

2.0

Mydriasis

1.8 (1.0)

1.5 (1.0-2.8)

1.0

Localized pain

1.4 (0.5)

1.0 (1.0-2.0)

1.0

Headache

1.4 (0.8)

1.0 (2.0-4.0)

1.0

Leukocytosis

1.4 (1.2)

1.0 (1.0-2.0)

1.0

Flushing

1.4 (0.9)

1.0 (1.0-2.0)

1.0

Increased CPK

1.4 (0.9)

1.0 (1.0-2.0)

1.0

Oliguria

1.3 (0.9)

1.0 (1.0-2.0)

1.0

Periorbital edema

1.2 (0.6)

1.0 (1.0-1.8)

1.0

Fever

1.2 (0.5)

1.0 (1.0-1.8)

1.0

Nausea

1.1 (0.4)

1.0 (1.0-2.0)

1.0

Regional lymphadenopathy

0.7 (0.5)

1.0 (0.0-1.0)

1.0

Transient hyperglycemia

0.4 (0.6)

0.0 (0.0-1.0)

0.0

Puncture marks

0.3 (0.5)

0.0 (0.0-1.0)

0.0

Nevertheless, for variables that the decimal of their means were close to 5 (e.g. flushing, leukocytosis), modes and medians were also taken into account. However, for hypokalemia with mean score of 2.5, the final score proposed by the focus group was 2, though the mode and median was 3 based on opinions of panel members (in Delphi process). This decision was mainly made due to the fact that generally hypokalemia can be better tolerated by the patients and easier to treat compared to hyperkalemia (17). Transient hyperglycemia and puncture marks did not receive any importance on describing the severity of envenomation and thus were not included in the initial draft. On the other hand, the feeling of pain in the entire affected limb was added to the initial draft (followed by the recommendation of focus group), though it was not present in the questionnaire. Some experts in the focus group believed that between localized pain and generalized body pain, another descriptor should exist to distinguish the pain at the bite site, the pain that spreads over the bitten limb and pain proposed score was 2 (between 1 for localized pain and 3 for generalized pain). After these modifications and also categorization of the clinical effects in system organs and adding definitions for ascertainment of the clinical effects, the final draft of LESS was developed (Figure 1).

 

Figure 1. Latrodectus Envenomation Severity Score

CPK: creatine phosphokinase, SBP: systolic blood pressure, DBP: diastolic blood pressure

Upper limit of CPK in various commercial kits my be different.   

Discussion

Latrodectism is a condition with intense clinical presentation that is mostly resolvable with proper treatments while very rarely results in death (2,3). Northeast part of Iran (Khorasan) is an endemic environment for Mediterranean black widow spider or Latrodectus tredecimguttatus (2,3,16,18). Its venom that mostly contains neurotoxins can induce neurotransmitter release from nerve endings and consequently facilitate calcium influx into the presynaptic neuron that leads to massive release of acetylcholine at the neuromuscular junction (1,19). This induces direct neurologic effects and reactive inflammatory responses. The severity of reactions and the envenomation syndrome in general will be lessened throughout the time. Nevertheless, an effective treatment can shorten this duration (8,9). However, whether the current recommended treatments such as analgesics and antivenom are meaningfully efficient on improving the patients and reducing the hospital stay or not have been subjects of controversy (10). In previous research done for evaluating the effectiveness of treatments for latrodectism, only scales for measuring the severity of an isolated clinical effect were used (9-11). This approach can be misleading, because the whole picture of the envenomation syndrome is neglected and not assessed. In the present study, a severity index for assessment of possible clinical manifestations of widow spider bite (in human subjects) has been developed for the first time. The scores have been allocated based on clinicians' global judgment on prognosis of widow spider victims. The Delphi process utilized in this evaluation assures that the resulting index represents the consensus of a group of experts in treating and research on widow spider bite envenomation (12,13).

In this measure, acute renal failure, myocarditis, pulmonary edema and ileus received the highest scores, though they are rare consequences of widow spider bite (4,5,20-23). However, they are potentially life-threatening for the victims. One of the deaths due to Latrodectus envenomation reported in Mashhad had developed ileus (3). Despite acute renal failure and myocarditis in latrodectism have been shown to be reversible, they entail more aggressive treatments and longer duration of hospitalization (4,5,22,23). Moreover, myocarditis due to widow spider bite caused one death in Madagascar; however, it was mainly due to limited facility (24). On the other hand, increased CPK that is a more common phenomenon in Latrodectus envenomation was among the items receiving the lowest score. The reason was that the rise of CPK in widow spider bite even in very high levels is simply resolvable and is unlikely to be clinically important or contribute to the rhabdomyolysis or acute renal injury (3,8). 

In the clinical practice, the management of Latrodectus envenomed patients is not dependent on the availability of the index for describing the severity of envenomation. However, the index can help junior physicians not to forget examining all the possible features of latrodectism. Hence, it can assist as a useful teaching tool for less experienced clinicians. In addition, the index can better describe and classify the profile of a series of patients and can serve as a reliable tool for comparing series of patients at different centers and in different published studies. Moreover, the LESS can be applied as a monitoring tool for assessment of worsening or improvement of the patient during admission. A scoring system that reliably monitors the clinical course would be able to provide purposive comparisons among different treatment approaches (25).

Limitations

The proposed version of the LESS index presented in this article has been mainly based on clinicians' judgment. This represents only the initial step of validation. This necessitates evaluation of the score validity by application of the index on widow spider victims in prospective studies. Moreover, the scores of some clinical items might be overestimated or underestimated by the panel members and thus calculating value of the score of each clinical item based on patients' prognosis in further studies is necessary. In this study, opinions and recommendations of experts in treating black widow spider bite, endemic in Khorasan region, were applied to develop the index. Participation of experts in Latrodectus envenomation from other parts of the world would probably gave more comprehensive results. 

Conclusion

The LESS is a new assessment tool that is designed to more objectively evaluate the severity and progression of envenomation in victims of widow spider bite. The prognostic-ability, reliability and sensitivity to change of the index should be investigated in future studies.

Acknowledgment

The authors would like to thank Dr. G. A. Zare, Dr. H. Khosrojerdi, Dr. O. Mehrpour, Dr. A. Ghassemi Toussi, Dr. B. Dadpour, Dr. Z. Oghabian, Dr. M. Maleki, Dr. K. Ghasempouri, Dr. A. Gharaie, Dr. M. Vahabzadeh and Dr. M. Khadem-Rezaiyan for their kind cooperation and recommendations.

 

Conflict of interest: None to be declared.

Funding and support: None.

  1. Peterson ME. Black widow spider envenomation. Clin Tech Small Anim Pract 2006;21(4):187-90.
  2. Isbister GK, Fan HW. Spider bite. Lancet 2011;378(9808):2039-47.
  3. Afshari R, Khadem-Rezaiyan M, Balali-Mood M. Spider bite (latrodectism) in Mashhad, Iran. Hum Exp Toxicol 2009;28(11):697-702.
  4. Kose A, Bozkurt S, Lok U, Zenginol M, Yildirim C, Gunay N, Kose B. Presumptive Latrodectus bite with ileus and myocardial involvement. Wilderness Environ Med 2010;21(3):271-2.
  5. Karcioglu O1, Gumustekin M, Tuncok Y, Celik A. Acute renal failure following latrodectism. Vet Hum Toxicol 2001z43(3):161-3.
  6. Maretić Z. Latrodectism: variations in clinical manifestations provoked by Latrodectus species of spiders. Toxicon 1983;21(4):457-66.
  7. Isbister GK, Gray MR. Latrodectism: a prospective cohort study of bites by formally identified redback spiders. Med J Aust 2003;179(2):88-91.
  8. Clark RF, Wethern-Kestner S, Vance MV, Gerkin R. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med 1992;21(7):782-7.
  9. Isbister GK, Brown SG, Miller M, Tankel A, Macdonald E, Stokes B, et al. A randomised controlled trial of intramuscular vs. intravenous antivenom for latrodectism--the RAVE study. QJM 2008;101(7):557-65.
  10. Isbister GK, Page C, Buckley N, Fatovitch D, Pascu O, Macdonald S, et al. Randomized Controlled Trial of Intravenous Antivenom Versus Placebo for Latrodectism: The Second Redback Antivenom Evaluation (RAVE- II) Study. In: Gawarammana I, Dawson A, Buckley N, Afshari R, Lau F, Al-Duaij N, et al. editors. Proceedings of 12th International Scientific Congress of Asia Pacific Association of Medical Toxicology; 2013 Nov 21-23; Dubai, United Arab Emirates. p. 86.
  11. Khosrojerdi H, Afshari R. Tramadol is Superior to Methadone in Black Widow Spider Envenomation; a Randomized Control Trial. In: Gawarammana I, Dawson A, Buckley N, Afshari R, Lau F, Al-Duaij N, et al. editors. Proceedings of 12th International Scientific Congress of Asia Pacific Association of Medical Toxicology; 2013 Nov 21-23; Dubai, United Arab Emirates. p. 81.
  12. Gustafson DH, Fryback DG, Rose JH, Yick V, Prokop CT, Detmer DE, et al. A decision theoretic methodology for severity index development. Med Decis Making 1986;6(1):27-35.
  13. Fink A, Kosecoff J, Chassin M, Brook RH. Consensus methods: characteristics and guidelines for use. Am J Public Health 1984;74(9):979-83.
  14. Hahn I. Arthropods. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, editors. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. p.1561-81.
  15. Graudins A. Spiders. In: Shannon MW, Borron SW, Burns MJ, editors. Haddad and Winchester’s clinical management of poisoning and drug overdose. 4th ed. Philadelphia: Elsevier; 2007. p. 433-9.
  16. Afshari R, Monzavi SM. Venomous animals and arthropods envenomation. In: Afshari R, Monzavi SM, editors. Afshari’s Clinical Toxicology and Poisoning Emergency Care. 2nd ed. Mashhad: Mashhad University of Medical Sciences Publication; 2012. p. 221-41.
  17. Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North Am 2005;23(3):723-47.
  18. Afshari R, Majdzadeh R, Balali-Mood M. Pattern of acute poisonings in Mashhad, Iran 1993-2000. J Toxicol Clin Toxicol 2004;42(7):965-75.
  19. Barry JD, Wills BK. Neurotoxic emergencies. Neurol Clin 2011;29(3):539-63.
  20. Gueron M, Ilia R, Margulis G. Arthropod poisons and the cardiovascular system. Am J Emerg Med 2000;18(6):708-14.
  21. Jelinek GA. Widow spider envenomation (latrodectism): a worldwide problem. Wilderness Environ Med 1997;8(4):226-31.
  22. Levine M, Canning J, Chase R, Ruha AM. Cardiomyopathy following latrodectus envenomation. West J Emerg Med 2010;11(5):521-3.
  23. Kara H, Ak A, Bayir A, Avci A. Reversible myocarditis after spider bite. BMJ Case Rep 2013 Apr 8;2013. pii: bcr2013008957.
  24. Ramialiharisoa A, de Haro L, Jouglard J, Goyffon M. Latrodectism in Madagascar. Med Trop (Mars) 1994;54(2):127-30. (In French)
  25. Boyle MH, Torrance GW. Developing multiattribute health indexes. Med Care 1984;22(11):1045-57.