Occult paraquat poisoning causing pneumomediastinum and organizing pneumonia

Abstract

Pneumomediastinum is not an uncommon manifestation of lung toxicity in acute paraquat ingestion. The condition is almost invariably seen with other lung parenchymal abnormalities such as consolidations, ground-glass opacities and interlobular septal thickening. The diagnosis may be challenging in cases with no history of toxin exposure, presentation with a subacute illness and/or absence of typical local or systemic features of paraquat toxicity.

Introduction

Pneumomediastinum describes the presence of air or gas in the mediastinum. The common predisposing conditions are chest trauma, oesophageal rupture, instrumentation of the airways or oesophagus, pulmonary disorders associated with alveolar rupture, excessive cough and severe acute asthma. ¹ Without any of these predisposing factors, interstitial lung diseases or lung infections are rarely complicated by pneumomediastinum. The condition is not an uncommon manifestation of lung toxicity in acute paraquat ingestion and is almost invariably seen with lung parenchymal abnormalities. However, the diagnosis may be challenging in cases with no history of toxin exposure, presentation with a subacute illness and/or absence of typical local or systemic toxicity features. ² Here, we present two young patients with progressive dyspnoea of subacute duration and pneumomediastinum and organizing pneumonia on high-resolution computed tomography (CT) of the thorax. Subsequently, a diagnosis of occult paraquat toxicity was made.

Case 1

A 20-year old male presented as an emergency with dry cough and progressive dyspnoea for 20 days. He had no fever nor other systemic symptoms. There was no history of pre-existing medical comorbidity or substance abuse. On examination, his respiratory rate was 36 breaths/min, pulse 110 beats/min and oxygen saturation 89% with low-flow oxygen supplementation. The examination of his skin and oral mucosa was unremarkable. Lung auscultation revealed diffuse crackles and bronchial breathing on both sides.

Laboratory investigation demonstrated a leucocytosis (25.2 × 10⁹/L) and elevated alanine transaminase (101 U/L, range 2–41). A thoracic CT scan showed pneumomediastinum and consolidations, ground-glass opacities (GGOs) and interlobular septal thickening in both lungs. Initially, the possibility of organizing pneumonia due to infection or interstitial lung disease was suggested, and antibiotics were administered. However, laboratory investigations for these disorders were unremarkable.

Discussion with the patient's close relatives revealed ingestion of herbicide paraquat dichloride (24% solution) with suicidal intention one month previously. After ingestion, the patient developed oral ulcers, difficulty swallowing and acute kidney injury. He was admitted to a local hospital, where he received conservative treatment, following which his acute kidney injury improved, and he was discharged.

A diagnosis of paraquat-related lung toxicity was made. The patient's oxygen requirement progressively increased. Methylprednisolone 1 g/d injection was commenced, but despite this, he succumbed after five days.

Case 2

A 23-year-old male was admitted as an emergency with a history of decreased urine output and progressive dyspnoea for 15 days. There was no history of medical comorbidity. However, he did use illicit drugs in both intravenous and inhalation forms. On admission, he was tachypnoeic (respiratory rate 32 breaths/min), with a pulse of 100 beats/min and oxygen saturation of 76% on ambient air. Lung auscultation revealed diffuse crackles.

Laboratory investigations demonstrated elevated serum creatinine (379.3 µmol/L, range 44.2–106.1), hyperbilirubinaemia (total 122.3 µmol/L, range 3.4–20.5; conjugated 93.9 µmol/L, range 0–5.1) and elevated liver transaminases (aspartate transaminases 249 U/L, range 2–40; alanine transaminases 219 U/L, range 2–41). A CT chest scan showed consolidations and GGOs in both lungs, a pneumomediastinum, mild pneumothorax and subcutaneous emphysema.

As in Case 1, given the negative initial diagnostic workup for infectious and non-infectious inflammatory disorders, the presence of organ failure triad of lung, liver and kidney, and characteristic CT findings, a possibility of paraquat poisoning was entertained. This was initially denied, but relatives related ingestion of paraquat dichloride (24% solution) 15 days previously for self-harm. Indeed, a careful oral examination showed a tongue coated with ulcers and slough. The patient received high-quality supportive care but died on the third day of admission.

Discussion

Paraquat is a widely used herbicide in agricultural communities of low-middle-income countries, such as India. ³ Severe systemic toxicity typically occurs following intentional or accidental oral ingestion, with mortality within 2–4 weeks in most cases. ⁴ The severe toxidrome after acute ingestion typically includes an organ failure triad of liver, kidney and lung, manifesting clinically as jaundice (conjugated hyperbilirubinaemia with elevated transaminases), acute kidney injury (requiring dialysis in many cases) and acute hypoxemic respiratory failure (typically requiring high-flow oxygen or mechanical ventilation), respectively. Because the history of toxin ingestion (suicidal or homicidal) may not be forthcoming in many cases, recognizing this organ failure triad remains paramount in daily emergency practice. ⁵ Moreover, given the corrosive nature of paraquat, ulceration of the oral cavity and upper gastrointestinal tract and slough formation over the tongue typically occur after acute ingestion but may be overlooked in a busy emergency department (as in our second case).^5,6 However, mild oral ulceration and non-severe acute kidney and liver injuries usually resolve within the first 2–3 weeks after ingestion, and beyond this period, respiratory failure typically predominates the clinical picture (such as in our first case). ⁷

The principal mechanism of paraquat-related pulmonary toxicity (also referred to as “paraquat lung”) is cellular damage of type 1 and type 2 pneumocytes by the generation of reactive oxygen species. ⁸ The initial destructive phase of lung toxicity is characterized by alveolar destruction, pulmonary inflammation, congestion and haemorrhage. After 1–2 weeks, the proliferative or cellular phase is hallmarked with the proliferation of the fibroblasts and the deposition of collagens, resulting in irreversible pulmonary fibrosis. ⁸

A CT chest scan in paraquat toxicity typically shows diffuse GGOs, consolidation and interlobular thickening in both lungs, mimicking organizing pneumonia. Pneumomediastinum is less common, seen in up to 40% of cases.^9,10 The two most accepted mechanisms for its development are air leaks from the perforation or rupture of damaged alveoli in fibrotic lung disease and oesophageal rupture due to corrosive injury.^6,9,10 Mild pneumothorax is often seen together with pneumomediastinum, and rarely, pneumoperitoneum is also present. ⁶ Pneumomediastinum may rarely occur without accompanying lung parenchymal abnormalities. The treatment is usually supportive with its spontaneous resolution. ⁶ The presence of pneumomediastinum is helpful in the prognosis of the toxidrome, with mortality up to 100% in some reports.^9,10

There is no specific antidote for paraquat toxicity, and evidence on available treatment options is lacking. Immunosuppressive therapy with systemic steroids and cyclophosphamide has been used with limited success. Haemoperfusion and haemofiltration have been advised in the early course of poisoning to reduce its concentration in the blood. ⁴

In conclusion, pneumomediastinum without the classical predisposing factors, in the background of GGOs, consolidation and/or interlobular thickening, is highly suggestive of paraquat lung in areas where this poisoning is prevalent. A detailed clinical history, careful examination of the oral cavity and recognition of organ failure triad of paraquat toxidrome are essential to make a timely diagnosis.