Paraquat Tongue: Rebirth of Paraquat Intoxication

Acute pesticide poisoning accounts for significant morbidity and mortality in the world, especially in developing countries. We present an interesting case of paraquat intoxication here. A 39-year-old man was brought to our emergency department (ED) by his family soon after attempting suicide by ingesting unknown substances. Initial vital signs, laboratory data, and chest radiography showed normal. Only green-blue color of finger and redness of tongue were noted. Urine unknown drugs screening tests were negative. Initial urine paraquat test was also negative at our ED. Then he con-fessed to taste 1-2 drips of paraquat (24%) through his right finger. We arranged hemoperfusion therapy due to the strong contact history and some physical examination findings. Finally, the serum paraquat level at ED was 0.1 μg/ml . This case highlights that even in cases with negative urine paraquat tests, detailed history taking and physical examination can help the diagnosis of paraquat poisoning. Early recognition and the appropriate treatment are imperative.


Introduction
The main causes of pesticide poisoning in Taiwan are paraquat, organic phosphates, glyphosate and carbamates [1,2]. Paraquat, 1, '-dimethyl-4,4'-bipyridinium dichloride, is the one of the most widely used herbicides in the world. Paraquat is a rapidly-acting, non-selective herbicide and relatively inexpensive. It is toxic to human beings and animals by its redox activity, which products superoxide anion, potentially leading to acute respiratory distress syndrome and acute kidney injury [3,4].
Paraquat is rapidly absorbed from ingestion, dermal exposure and inhalation and can be detected within 1 hour from serum and uri-ne. According to data published by Proudfoot et al. (1979), Proudfoot (1995) and Smith (1988b), peak concentrations (Cmax) in humans are attained within 2 hours to 4 hours after ingestion [6,7]. Irrespective of the route of administration, lung and kidney are the organs showing the highest concentrations of paraquat [7][8][9]. Preferential accumulation in the lung is increasing toxicity due to superoxide anion. Over a period of hours to days, these processes cause multi-organs failure. The most affected organs are those with oxygen tension, high blood flow, and energy requirements, in particular the heart, lung, kidney, and liver. In general, urine paraquat test is useful for screening paraquat poisoning [10]. Management of paraquat intoxication usually depends on the amount ingested and the time elapsed since the exposure.

Case Report
A 39-year-old male was brought to our emergency department (ED) 2 hours after attempting suicide by ingesting unknown herbicides. He has history of depressive disorders without regular follow-up. His Glasgow Coma Scale (GCS) is E4V5M6. His blood pressure was 130/96 mmHg, pulse rate was 82 beats/min, and respiratory rate was 18 breaths/min. Initial laboratory examinations revealed normal kidney function tests and normal serum electrolytes. Unknown drugs screening test of urine, including benzodiazepine, tricyclic antidepressants, barbiturates, cocaine, acetaminophen, tetrahydrocannabinol and phencyclidine, showed negative results. Physical examinations revealed mild green-blue color over distal phalanx of right index finger (Figure 1). In addition, mild reddish without obvious ulceration was noted over the apex of tongue. Chest radiography was unremarkable. Urine paraquat test was also performed but revealed negative findings at initial 1 hour and 2 hours after arrival of ED. He received gastric lavage with NG-tube, and only some yellowish gastric juice was found from NG tube.
The patient finally told the physician that he took a small amount of paraquat (24%) through his right finger. The diagnosis of paraquat intoxication was made based on history taking and physical examinations. Then serum paraquat test was checked at ED. After admission, he received charcoal hemoperfusion therapy for 2 times. The apex region of tongue revealed mild reddish at day 3 ( Figure 2) and obvious ulcerations at day 6 ( Figure 3) after admission. Initial   serum paraquat test at ED was positive and the concentration was 0.1 μg/ml. Following kidney function tests and chest radiographies showed normal. The results of serials of serum paraquat concentrations were undetectable after hemoperfusion. Lastly, he was discharged after 10 days in hospital. No obvious respiratory sequelae and kidney injury were found with 6-month follow-up.

Discussion
Paraquat intoxication is life-threatening and can cause major effects on gastrointestinal tract, lung, liver, and kidney. The Median Lethal Dose (LD50) in human beings is approximately 35 mg/kg, which translates into as little as 8-12 ml of a 24% solution [11]. The gastrointestinal tracts such as tongue, mouth, pharynx, esophagus, stomach and intestine are the most initial sites of toxicity, which is manifested by edema, swelling, and painful ulceration. In some severe cases, centrizonal hepatocellular injury can occur, resulting in elevated bilirubin and enzymes like aspartate transaminase (AST), alanine aminotransaminase (ALT) and lactate dehydrogenase (LDH) [12]. The hepatic injury from paraquat can be severe enough to cause jaundice. However, he-patotoxicity is rarely a major determinant to clinical outcome. On the contrary, acute kidney injury plays a critical role in determining the clinical outcome [12].
Pulmonary complication also represents the most lethal and least treatable manifestation. Both type I and II pneumatocytes appear to selectively accumulate paraquat. Biotransformation of paraquat in these cells causes free radical production with promotion lipid peroxidation and cell injury [13,14]. There is a progressive decline in arterial oxygen tension and CO2 diffusion capacity. Cyanosis and dyspnea reflect deteriorating gas exchange in the damaged lung. In addition, frothy sputum is the early and principal manifestation of pulmonary edema. Such a serious dysfunction of gas exchange results eventual death due to hypoxemia. Acute pulmonary edema and early lung damage can occur within few hours to days after ingestion [13,14]. In clinical practice, routine investigations such as liver function tests, kidney function tests, and electrolytes are checked only to monitor baseline status of the patient. Several studies predicted survival rates in patients with paraquat intoxication by using plasma paraquat concentrations and/or clinical criteria [16][17][18][19].
Paraquat is not metabolised and nearly excreted unchanged in the urine, it can be easily detected by qualitative urine analysis. A semi-quantitative test using bicarbonate and sodium dithionite can be used as a bedside test to confirm systemic paraquat toxicity [19]. In an alkaline medium, sodium dithionite reduces paraquat to a blue radical. If the urine paraquat concentration is more than 1 μg/ml, the urine will appear blue and this finding alone indicates a very poor prognosis [20]. However, negative urine paraquat test could also be fatal [21]. To date, hemoperfusion is proven to be better than homodialysis in treating patients with paraquat poisoning. Hemoperfusion can decrease mortality rates within 6-12 hours after paraquat exposure. Cyclophosphamide, methylprednisolone,

Conclusion
The present case highlights the importance that physicians should be alert to the possibility of acute paraquat poisoning in high risk patients presenting with unknown skin lesions and mucosal ulcerations. The absence of paraquat in urine could also be fatal. Early recognition and the rapid treatment of paraquat intoxication are imperative, even in cases with negative urine paraquat tests.