CME INDIA Case Presentation by Dr. Somnath, Director & Chief Diabetes-Medicine-Critical Care, Hyderabad Medical Centre.
CME INDIA Case Study
How presented?
- 32-year-old male presented with mild salivation. No past history of comorbidities. There is history of accidental Paraquat ingestion 15 days back.
- Examination of the tongue displayed.
- All viral Markers-Negative, On Diabetic.
- All target organs evaluated-Normal.
- No Pharyngeal Ulcer.
Examination of the tongue
What is the diagnosis?
Video
CME INDIA Discussion
Diagnosis
Dr. Rajiv, Associate Professor of Dermatology, JLNMCH, Bhagalpur:
- This case is, what is called, “Paraquat Tongue.”
- There are multiple ulcers of varying severity over the tongue and many of them are in healing process. Erythema is of moderate degree.
- For 2 weeks, have elapsed and there are no comorbidities, indicating that probably the agent was taken in a very little amount and that was also “spit out” from the mouth itself and not ingested. Thereby no/ minimal absorption took place.
- It is worth to examine any mucosal affection of pharynx, oesophagus or stomach.
- Nevertheless, a thorough exam of lungs, kidneys, liver and heart is mandatory.
- Presence of Mucosal lesions in the oral cavity and absence of such lesions in the pharynx, oesophagus and stomach are an indication, that the substance was not ingested and was probably spit out from the mouth itself.
How to manage further?
Dr. Rajiv, Associate Professor of Dermatology, JLNMCH, Bhagalpur:
- Paraquat has corrosive properties and is highly irritant to mucosa, when it comes into contact with it. So, there is, ” Irritant Contact Dermatitis”. (ICD)
- For 2 weeks, have already passed and lesions aren’t appearing so aggressive, this case may be treated as per the lines of ICD.
- Kenacort Oral Paste + Mucopain Gel, to apply at least 2-3 times daily.
- Antioxidants, to take orally daily. Metronidazole, Bland mouth wash.
- Supportive steps.
- These measures may help, the problem to resolve faster.
Dr. N. K. Singh shares:
- Paraquat is a toxic herbicide.
- It is widely used by Indian farmers for killing weeds.
- It is easily available in rural areas for deliberate self-poisoning.
- The actual ingestion of paraquat or spitting it without swallowing results in a typical tongue change called “Paraquat tongue.”
Typical Paraquat Tongue
| The tongue lesions start with redness and gradually progressed to painful erosions and ulcers. |
| Examination of tongue may reveal multiple erosions and superficial ulcers, few of which coalesced. |
| Floor of the ulcers may be covered with yellowish necrotic debris. |
| Centre of the tongue may be relatively spared. |
| The mucosal involvement is universal in paraquat poisoning. Initially, tongue becomes erythematous and swollen but later develops erosion and ulcerations which are often covered with yellowish necrotic debris (Paraquat tongue). |
How to treat tongue ulcers?
| The management of paraquat tongue includes: |
| Daily debridement of slough. |
| Topical application of benzocaine, choline salicylate, benzalkonium chloride and contents of multivitamin capsules. |
| The tongue lesions can be managed by topical application of 20% benzocaine, povidone iodine mouth gargle and topical metronidazole 1% and chlorhexidine 0.25% combination oral gel. |
| Early insertion of a nasogastric feeding tube ensures adequate nutrition (as needed). |
CME INDIA Learning Points
By Dr. Shiney Aggarwal, M. D. (Internal medicine), Medical Specialist, Civil Hospital Khanna, Ludhiana, Punjab.
Paraquat
- l-l-dimethyl-4-4’-bipyridine.
- Synthetic, non-selective contact herbicide.
- Formulations used in the field range from 0.07% to 0.14%.
- Paraquat, when ingested, is highly toxic to mammals, including human without specific antidotes.
- LD50 in humans is approximately 3-5 mg/kg, which translates into as little as 10-15 mL of a 20% solution.
Mechanism of Toxicity
- Paraquat-induced toxicity is a manifestation of its ability to undergo redox-cycling and subsequent generation of reactive oxygen species (ROS)
- Generation of highly reactive oxygen and nitrite species results in toxicity in most organs but the toxicity is particularly severe in the lungs as paraquat is taken up against a concentration gradient in to the lung
- Paraquat is metabolized by several enzyme systems like NADPH-cytochrome P450 reductase, xanthine oxidase, NADH-ubiquinone oxidoreductase and nitric oxide synthase
- The multiplicity of pathway of metabolism may be the underlying explanation for the observation that no agent aimed at any particular mechanism has been shown to alter toxicity substantially when given after poisoning
- Rather treatments are aimed at more non-specific secondary pathological processes such as inflammation
- Paraquat is metabolized by several enzyme systems like NADPH-cytochrome P450 reductase, xanthine oxidase, NADH-ubiquinone oxidoreductase and nitric oxide synthase
- The multiplicity of pathway of metabolism may be the underlying explanation for the observation that no agent aimed at any particular mechanism has been shown to alter toxicity substantially when given after poisoning
- Rather treatments are aimed at more non-specific secondary pathological processes such as inflammation
- Although pulmonary toxicity occurs later in paraquat poisoning than other manifestations, it is the most severe
- They are most lethal and least treatable manifestation of toxicity
- Acute alveolitis, vascular congestion, adherence of activated platelets and polymorphonuclear leucocytes, apoptosis
- Destructive phase: both type of pneumocytes demonstrate swelling, vacuolation and disruption of mitochondria. It is associated with pulmonary edema
- Proliferative phase: alveolar space is filled with mononuclear profibroblasts which mature into fibroblasts over days to weeks. It results in lung fibrosis.
- Kidneys: damage to proximal tubule occurs and is often reversible
- GIT: site of initial toxicity after ingestion. Manifest as swelling, edema, painful ulceration of mouth, pharynx, esophagus, stomach and intestine. At high level of toxicity, it can lead to centrilobular hepatocellular injury with elevated liver enzymes and bilirubin
- Focal necrosis of myocardium and skeletal muscle
- Cerebral edema and brain damage
- Local skin damage occurs as contact dermatitis
Clinical Course
- GI toxicity is universal in those ingesting paraquat
- Paraquat tongue
| Poisoning |
| Mild or subacute AMOUNT < 20-30 mg/kg body weight SYMPTOMS Asymptomatic or mild GI symptoms Renal or hepatic lesions are minimal Decrease in pulmonary diffusion capacity present Complete recovery expected |
| Moderate to severe AMOUNT >20-30 but<40-50 mg/kg body weight SYMPTOMS Immediate: vomiting Hours: diarrhea, abdominal pain, mouth & throat ulceration 1-2 wks.: cough, hemoptysis, pleural effusion, pulmonary fibrosis Survival is possible but, in most cases, death occurs within 2-3 wks. from pulmonary failure |
| Fulminant or hyperacute AMOUNT >40-50 mg/kg body weight SYMPTOMS Immediate: vomiting Hours to days: diarrhea, abdominal pain, renal and hepatic failure, GI ulcer, pancreatitis, toxic myocarditis, refractory hypotension, coma Death from cardiogenic shock and multiorgan failure within 1-4 days |
Management
- Diagnosis: history or evidence of ingestion, clinical signs
- First aid initiated without delay
- Assess and manage airway, breathing, circulation
- AVOID OXYGEN
- Mild to moderate hypoxia should not be routinely treated as oxygen may worsen oxidative stress
- Qualitative test
- Urine spot test: bicarbonate and sodium dithionite, reduces paraquat to blue radical. Blue urine indicates paraquat concentration > 1mg/l, indicates poor prognosis
- Negative test should be repeated 6 hours post ingestion & if still negative then serious sequelae unlikely
- GI decontamination
- Gastric lavage?? (Contraindicated in caustic injury)
- Activated charcoal (50-100 g for adults) or Fuller’s earth (15% suspension)
- Early management
- IV fluids
- Analgesia
- Mouth care
- Nil by mouth
- Early insertion of nasogastric tube with caution to avoid mucosal injury
- Subsequent management
- Analgesia
- Antibiotic for supervening infection
- Hemodialysis
- Palliative care
- Monitoring
- Daily fluid balance maintained ensuring good urine output without fluid overload
- Jaundice and right hypochondrial pain for liver toxicity
- Resp rate, SpO2, crepitations for respiratory failure
Credit: Iyyadurai, Ramya. and Mohan, Jambugulam. and Jose, Arun. and Das, Sohini. and Johnson, Jacob. and Gunasekaran, Karthik. Paraquat poisoning management. Current Medical Issues, 2019.
Elimination enhancement: hemodialysis/ hemoperfusion
- Should be considered in patients who have developed symptomatic acute renal failure
- Since the prognosis of these patients is generally poor, so unlikely to change overall outcome
Other Options
Immunosuppression
- To suppress acute inflammatory process associated with paraquat poisoning
- Cyclophosphamide, MESNA, methylprednisolone, dexamethasone, Antioxidants
- Vitamin E: membrane stabilization of polyunsaturated fatty acids and ROS scavenging
- Vitamin C: donates electron to free radicals thereby neutralizes them
- N-acetylcysteine: reduces paraquat induced apoptosis and inflammatory process
- Deferoxamine
- Salicylic acid
CME INDIA Tail Piece
- The popular herbicide paraquat has been used on crops in the United States since the 1960s, but lawsuits say exposure to the toxic chemical can cause Parkinson’s disease in farmers and other agricultural workers.
- It’s a popular herbicide because it effectively clears fields of unwanted weeds and grasses, but paraquat is known to be highly toxic. Ingesting paraquat can cause acute multiple organ failure that can be fatal.
- In fact, according to the U.S. Environmental Protection Agency, “one sip can kill.”
- More than 32 countries have banned the herbicide, including the European Union, according to Parkinson’s News Today. While the U.S. Environmental Protection Agency hasn’t banned the chemical, its use is restricted to licensed, trained applicators.
- Now several manufacturers face lawsuits filed by people who claim exposure to paraquat led them to develop Parkinson’s and lawyers across the country are accepting cases.
Parquat and Parkinsonism Link?
- Systematic searches on the topic of paraquat and Parkinson’s disease including those on the broader topic of environmental and occupational risk factors for Parkinson’s disease (269 publications opined that it has been not established so far that exposure to paraquat causes Parkinson’s disease.
- Thus, a consensus exists in the scientific community that the available evidence does not warrant a claim that paraquat causes Parkinson’s disease.
References:
- Iyyadurai, Ramya. and Mohan, Jambugulam. and Jose, Arun. and Das, Sohini. and Johnson, Jacob. and Gunasekaran, Karthik.Paraquat poisoning management.Current Medical Issues,2019, 17:2,34-37.doi = {10.4103/cmi.cmi_29_19}
- Berry, C., La Vecchia, C. & Nicotera, P. Paraquat and Parkinson’s disease. Cell Death Differ 17, 1115–1125 (2010). https://doi.org/10.1038/cdd.2009.217
- Douglas L. Weed,Does paraquat cause Parkinson’s disease? A review of reviews,NeuroToxicology,Volume 86,2021,Pages 180-184,ISSN 0161-813X,https://doi.org/10.1016/j.neuro.2021.08.006.
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Very informative