Hornet Sting-Induced Toxic Hepatitis

To the Editor:

Insect stings can produce symptoms ranging from mild local reactions to severe anaphylaxis. The four major stinging insects are bee, wasp, hornet, and yellow jacket, all of which are members of the order Hymenoptera. Unusual reactions reported after insect stings include serum sickness, neurologic disease, renal disease, and delayed hypersensitivity-type reactions 1. However, isolated acute hepatitis has been rarely reported. Here we report a case of acute hepatitis following multiple hornet stings and discuss the possible mechanisms underlying toxic hepatitis.

A 50-year-old man had a history of chronic hepatitis B, but normal liver function was documented during the outpatient follow-ups. He presented to our hospital after being stung by more than 200 hornets. He had been fishing near a river where he accidentally disturbed a hornet nest hanging in a tree. He was stung by more than 200 hornets over his nuchal area and bilateral upper arms, causing immediate and intense pain. No anaphylactic shock was noted during the ambulance transport. Upon arrival, his blood pressure was 150/90 mmHg, and he was in no apparent respiratory distress. He denied prior hornet stings, alcoholism, or drug use. The hornet was identified as Vespa affinis using colored insect atlas. Physical examination revealed icteric sclera and numerous sting wounds with swelling over his upper arms and nuchal area. Laboratory data, obtained 4 h after being stung, showed normal complete blood cell counts and markedly elevated aminotransferase levels. His initial serum alanine aminotransferase (ALT) was 1390 U/L and aspartate aminotransferase (AST) was 1457 U/L. His activated partial thromboplastin time (aPTT) was prolonged to 115 sec (control 36 sec), but his prothrombin time (PT) was normal.

Results of serial liver function tests and coagulation profiles, obtained after admission to the hospital, are displayed in Figs. 1 and 2. The observed maximum level of ALT was 3156 U/L, AST 3006 U/L, alkaline phosphatase (ALP) 626 U/L, gamma glutamyl transpeptidase (GGT) 567 U/L. The total bilirubin checked on the second day was 10 mg/dL and declined gradually afterward. The time to the observed peak levels was 1 day for aPTT and 2 days for AST, ALT, ALP, and GGT. Tests for disseminated intravascular coagulation, including fibrinogen degradation products and D-dimer, were negative.

Fig. 1. Serial measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) after the hornet sting.

Fig. 2. Serial measurements of total bilirubin (T-Bil) and coagulation profiles including prothrombin time (PT, shown in second), international normalized ratio (INR), and partial thromboplastin time (aPTT, shown in second) after the hornet sting.

Acute toxic hepatitis caused by hornet sting was highly suspected. Viral hepatitis profiles, including IgM Anti-HAV, anti-HBs, anti-HCV, HBeAg, and IgM anti-HBc were all negative, excluding other possible causes of acute liver damage. A positive HBV surface antigen was detected with a low HBV DNA level of 23.7 pg/mL, suggesting the unlikely possibility of acute exacerbation of chronic hepatitis B. Abdominal sonography only revealed a fatty liver. No renal failure, hemolysis, thrombocytopenia or rhabdomyolysis was noted throughout his hospital course. His wound pain and pruritus were treated with cold compressants, oral antihistamines, and analgesics. With supportive treatment, the patient's liver function tests improved markedly within 4 days, and he was discharged 1 week later.

This case demonstrates two unique characteristics of toxic hepatitis. First, the latent period between toxin exposure and liver injury in toxic hepatitis is usually short, usually within several hours 2. In our case, markedly elevated aminotransferase levels were documented 4 h after the hornet sting. Second, toxic hepatitis occurs with a predictable clinical picture in individuals exposed to the toxin and is dose-dependent 2. Multiple or massive stings by hornets can be fatal in children 3&4 but may cause less severe toxic hepatitis in adults if dose-dependent relationship exists. The common findings of the two child fatalities were massive hemolysis, coagulopathy, rhabdomyolysis, acute renal failure, encephalopathy, and hepatotoxicity 3&4. More observations through case series are necessary to determine whether multiple stings cause a less severe hepatic toxicity in adults.

Mechanisms to account for toxic hepatitis from hornet venom have been studied using the experimental model of rat liver. Envenomation with different doses of hornet's (Vespa orientalis) venom sac extract can induce enzymatic changes, including a 24-fold rise of ALP, 6-fold rise of ALT, and 9-fold rise of AST activity 5. This study concluded that hornet's venom is a predictable hepatotoxin causing a cholangiocellular pattern of enzymatic changes 5. Investigation by light microscopy and histochemistry showed foci of hepatocyte necrosis, fat infiltration, and increased alkaline phosphatase activity 6. Electron microscopy subcellular analysis showed the destruction of the mitochondira in the hepatocytes and damage to membrane of bile canaliculi, resulting in both hepatocellular damage and cholestasis in the rat model 6&7. These features of envenomation in the experimental studies are very similar to those found in our case.

Mild coaguloapthy with prolongation of aPTT and normal PT was observed in our case. Similar coagulation changes have been reported in vitro by Petroianu et al. 8. Their study of coagulation abnormalities after bee stings demonstrated rising PTT and decreasing PT after administration of various bee venom phospholipase A2 concentrations in vitro. However, prolongation of both PT and aPTT has also been reported with envenomation by Vespa orientalis, exhibiting serine and metaloprotease activities in vitro 9.

In conclusion, the current report presents a unique case of hornet sting–induced acute toxic hepatitis in an adult. Clinical toxicity consisted primarily of hepatocellular injury, conjugated hyperbilirubinemia, and mild coagulopathy. This case also highlights the heterogeneity of hornet sting–related toxicity and questions whether the toxicity is less severe in adults. Supportive treatment in this case led to complete recovery of hepatotoxicity.