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Every year, more than 1 million cases of scorpion envenomation are reported worldwide.1 Although the resultant mortality is lower than that from snake envenomation, there is substantial morbidity and, among children, a risk of death. Almost all systemic scorpion envenomation causes pain at the site of the sting. A mixed autonomic excitation (neuroexcitatory) syndrome that is unique to scorpions follows; the syndrome varies in type and severity according to the type of scorpion.2-4 In addition, a cytotoxic envenomation syndrome has been reported in areas of Iran in whichHemiscorpius lepturus is endemic.5

EPIDEMIOLOGY

Although millions of scorpion stings occur annually,1 most cases are minor, with localized pain and minimal systemic involvement.6,7 However, severe envenomation is a major public health problem in certain parts of the world — Central and South America, North Africa, the Middle East, and South Asia. Most scorpions that cause serious medical problems belong to the Buthidae family, which includes scorpions from the genera leiurus in the Near and Middle East, androctonus and buthus in North Africa, tityus in South America, centruroides in North and Central America, mesobuthus in Asia (especially India), and parabuthus in South Africa (for further information on several species in these genera, see Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org).1

In Mexico, probably hundreds of thousands of stings by centruroides scorpions occur each year. Similar numbers of cases occur in other areas where scorpions are endemic (e.g., in Tunisia2 and other parts of North Africa and in India8).

MECHANISMS OF ENVENOMATION AND PATHOPHYSIOLOGY

Scorpions have a stinger (or telson) in their tail (terminal segment) that contains venom glands. The scorpion hooks the tail over its body, which allows the stinger to penetrate the skin and inject venom. Numerous toxins have been identified in scorpion venoms, most of which are small peptide toxins that target ion channels found in both mammals and insects.9 The toxins that have the greatest medical consequence are the scorpion α-toxins, which consist of 61 to 76 polypeptides that bind to a specific site on the mammalian voltage-gated sodium channel. Once the toxin binds to a site, it inhibits the inactivation of the channel, which results in prolonged depolarization and, hence, neuronal excitation. Other toxins in scorpion venom act on potassium and calcium channels, but these toxins appear to be less important in human envenomation.9

Neuronal excitation stimulates autonomic centers, both sympathetic and parasympathetic, which results in autonomic excitation.9 In addition, scorpion α-toxins cause massive endogenous release of the catecholamines epinephrine and norepinephrine, as well as other vasoactive peptide hormones, such as neuropeptide Y and endothelin-1.10 As compared with sympathetic effects, parasympathetic effects are less severe; when they occur, they are often seen soon after the sting, and they may contribute to respiratory impairment. In contrast, the combination of sympathetic excitation and the release of catecholamine in plasma causes the majority of the severe systemic effects, including myocardial injury, pulmonary edema, and cardiogenic shock (Figure 1
). 

There is an initial increase in blood pressure and cardiac output, followed by decreasing left ventricular function and hypotension. The mechanisms of cardiac dysfunction and pulmonary edema after scorpion envenomation are complex, but they appear to result from a combination of catecholamine-induced myocarditis and myocardial ischemia (coronary vasoconstriction) and, possibly, a direct effect of toxin on the myocardium.11

The direct effects of scorpion toxins on the neuronal sodium channels of the somatic and cranial nervous system cause the classic neuromuscular excitation seen after stings by scorpions in the Americas, such as centruroides species. Central nervous system effects are uncommon and are generally related to the effects of severe envenomation because the toxins cannot cross the blood–brain barrier.

CLINICAL MANIFESTATIONS OF SCORPION STINGS

DIAGNOSTIC INVESTIGATIONS

There are no specific diagnostic investigations recommended for scorpion stings; in the majority of cases, no investigation is required, particularly in the many regions of the world where it is difficult to perform diagnostic tests.Investigations should focus on potential complications of scorpion envenomation; for example, creatinine levels should be measured to assess whether renal failure has occurred, and levels of pancreatic enzymes should be measured to determine whether the sting has induced pancreatitis. Serum scorpion venom levels have been measured in a number of research studies, but such assays are neither generally available nor useful in determining the appropriate treatment. In cases of severe systemic envenomation, an electrocardiogram should be obtained when possible, since electrocardiographic abnormalities are fairly common. Further investigation with echocardiography, assessment of serum markers of cardiac distress, and other investigations of the heart should be guided by the severity of the envenomation and the resources available.

TREATMENT OF STINGS AND THE ENVENOMATION SYNDROME

Numerous treatments have been recommended for scorpion envenomation, including antivenom, prazosin,8 inotropic agents,2 atropine, vasodilators, and benzodiazepines (Table 1 and Table 2
).12

However, the evidence for the effectiveness of most treatments is variable, and types of treatment appear to vary according to region.8 In severe envenomation, the standard intensive care treatment for acute pulmonary edema and cardiogenic shock appears to be appropriate and often includes the use of inotropes and specific vasodilators (Table 1 and Table 2). Symptoms related to the site of the sting should be managed with appropriate analgesia with acetaminophen and antiinflammatory agents, depending on severity (Table 1).

The use of antivenom for scorpion stings remains controversial, since the results of clinical trials have been both negative and positive. A large study from Tunisia showed no benefit from the routine administration of antivenom.6 However, that trial did not include many cases of severe or systemic envenomation, in which antivenom would be more likely to have beneficial effects. In contrast, in a small North American clinical trial of centruroides scorpion envenomation (15 patients), neurotoxic effects of envenomation resolved within 4 hours in all 8 patients who received antivenom as compared with only 1 of 7 patients who received placebo.12 In a randomized, open-label study in India involving 70 patients who had been stung by the red scorpion (Mesobuthus tamulus), the patients who received antivenom and prazosin had a more rapid recovery than did those who received prazosin alone.8 A recent study of red scorpion envenomation in 50 children also compared the use of antivenom and prazosin with prazosin alone and showed that the children who received antivenom plus prazosin had a more rapid recovery (mean between-group difference, 9 hours), were less likely to undergo progression to severe envenomation syndrome, and needed less prazosin than the children who did not receive antivenom.14

Although the evidence in favor of antivenom is heterogeneous, given the small size of the trials with positive results and the different scorpion species across studies, the reports, when taken together, suggest that administration of antivenom after a sting is of some benefit — a suggestion that is supported by recent observational studies of antivenom after stings by centruroides species.23,24 A cost-effectiveness analysis of the use of antivenom for scorpion envenomation in the United States showed that at its current price, antivenom is not cost-effective and that its use should be restricted to cases of severe envenomation.25 However, once severe envenomation has developed, the administration of antivenom may be less effective, since its primary therapeutic action is to bind toxins; it does not reverse established pathophysiological injury, such as excess levels of catecholamine, pulmonary edema, and cardiogenic shock. 10 (A list of the major scorpion antivenoms manufactured worldwide can be found athttp://wikitoxin.toxicology.wikispaces.net/Scorpions.) 

SUMMARY

Scorpion stings and envenomation are of clinical importance worldwide, and although most stings cause only local effects, severe envenomation that causes either excessive autonomic activity and cardiovascular toxic effects or neuromuscular toxic effects results in illness and, in the case of children, in death. The specific treatment is the administration of antivenom combined with symptomatic and supportive treatment, including prazosin and dobutamine in patients with cardiovascular toxic effects and benzodiazepines when there is neuromuscular involvement.