Historically, the red fire ant S. invicta was imported from South America into North America, residing in the soil of potted plants that were shipped in the 1930s. Since approximately the year 2000, the imported fire ant (IFA) has also been found in China and Taiwan. It belongs to the insect order Hymenoptera, which includes Formicidae (ants), Vespidae (wasps, hornets, and yellow jackets), and Apidae (honey bees and bumble bees) [3, 4]. The venom composition of the IFA is complex, including several proteins capable of inducing allergy and anaphylaxis. In addition to these proteins, piperidine alkaloids are also present and are a major component of IFA venom (approximately 95%) . This component is not allergenic but is responsible for the local pain and pustules commonly experienced in ant bites. After fire ant bites, three different reactions may be elicited: local, large local, or systemic (anaphylaxis) [6–9]. A local reaction results in an immediate flare and wheal followed by a pustule after approximately 1 day. A large local reaction is an erythematous, oedematous, and indurated region extending beyond the pustule, which may last several days. The occurrence rate of serious systemic reactions is much rarer, at approximately 2%.
The above complications relate to the biological activity of the ant venom, which causes cytotoxic, neurotoxic, and haemolytic reactions within the body [10, 11]. It also activates coagulation and predisposes the individual to a hypercoagulable state [12–14]. Javors et al. discovered that fire ant venom alkaloids affect certain physiological and biochemical functions of human platelets and neutrophils in 1993 . He found that venom alkaloids induced an increase in platelet intracellular calcium ion concentration (Ca2+), secretion of dense granules, and aggregation. The aggregation response was less complete than that of the platelet-activating factor (PAF). Furthermore, pre-treatment of platelets with venom alkaloids produced enhanced PAF-related intracellular Ca2+ spiking, suggesting synergism between the two agonists. Venom alkaloids also induce an increase and accumulation of neutrophils and intracellular Ca2+. These results suggest that fire ant venom alkaloids do activate platelets and neutrophils. Therefore, platelet thrombi formation and endothelial injury may occur in vivo after fire ant bites. In fact, there is a report on a 5-day-old neonate developing microangiopathic haemolytic anaemia after fire ant bites . These findings may partially explain the pathogenesis of HUS following exposure to fire ant venom. There are some case reports of HUS or ADAMTS-13 deficiency after scorpion sting [16–19]; however, to the best of our knowledge, there are no existing reports of HUS development as a result of ant bites.
The limitation of our report is that we cannot examine the complement regulators, genetic mutations, or ADAMTS 13 activity in this patient. Therefore, the possibility of atypical HUS and TTP cannot be completely excluded. The diagnosis of atypical HUS is substantially one of exclusion, based on evidences of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure, in the absence of infections by Shiga-toxin producing bacteria or other micro-organisms associated with HUS, of possible causes of secondary forms of HUS (such as medications, autoimmune diseases, and malignancy) and of reduced ADAMTS 13 activity (< 10%) . Atypical HUS designates a primary disease due to a disorder in complement alternative pathway regulation. The onset is from the neonatal period to adult [20, 21]. At the first episode of HUS, about one-third of patients have progressed to end-stage renal disease and half of the patients have relapses. Gene mutations—including complement regulatory proteins thrombomodulin, factor H, factor I, and membrane cofactor protein (MCP)—have been demonstrated. Mutations in the genes for C3 convertase proteins, C3 and factor B, as well as patients with anti-factor H antibodies, have also been reported [20, 21]. The disease is familial in approximately 20% of pedigrees. Recent studies have showed that the complement abnormalities, such as reduced C3 levels, reflecting activation of complement alternative pathway, are found only in a subset of patients, and are not necessary to make the diagnosis of atypical HUS [20, 22]. Although our patient didn’t have HUS-like episodes family history and had normal serum C3, C4 levels, we still cannot rule out a putative role of complement dysregulation in the pathogenesis of this case. ADAMTS 13 activity is typically decreased or absent in thrombotic thrombocytopenic purpura (TTP) patients, and is a good marker for differential diagnosis between TTP and atypical HUS. There has been a case report of ADAMTS 13 deficiency after a scorpion sting and successful recovery after treatment by plasma exchange . And, a consistent subset of patients with severe ADAMTS13 deficiency (e.g. 29% in the series of 65 patients from the Oklahoma TTP-HUS Registry presented by JN George) has no neurological symptoms . The clinical features of TTP are similar to those of our case, so we think although there were no neurologic symptoms (including headache, dysphasia, seizure, confusion, stupor, or coma) in our patient; TTP remains a possible differential diagnosis unless normal ADAMTS13 activity is proved.