Pneumocystis Pneumonia Infection in a Survivor of Paraquat Intoxication

Abstract

Patients who survived recent paraquat intoxication might be treated with glucocorticoid andcyclophosphamide to avoid further lung fi brosis. Such patients might be susceptible to opportunistic infections. Pneumocystis pneumonia (PCP) is an important opportunistic lung infection in hematologic malignancy patients on chemotherapy. We report a patient who recently survived paraquat intoxication and presented with acute respiratory insuffi ciency post glucocorticoid and cyclosporine treatment. A fulminant clinical course, and a clear medical history of immunocompromised state draw physician’s attention to the possible opportunistic lung infection. PCP infection was confi rmed by a PCP deoxyribonucleic acid test. The symptoms improved markedly after appropriate antibiotics treatment. This report suggests that clinicians should consider PCP infection in patients who develop secondary pneumonia after paraquat intoxication. PCP treatment as part of empirical antibiotics should be added, especially in such patients presented with rapidly progressive course.

Introduction

Patients who survived recent paraquat intoxication might be treated with glucocorticoid and cyclophosphamide to avoid further lung fibrosis.[1] The accumulation of paraquat in the lungs leads to diffuse alveolitis, followed by extensive pulmonary fi brosis.[2] Such patients might be susceptible to opportunistic infections. Pneumocystis pneumonia (PCP) is an important opportunistic lung infection in hematologic malignancy patients on chemotherapy.[3] PCP infection became prevalent with the spread of Human Immunodefi ciency Virus (HIV) infection.[4] In the absence of HIV infection, the mortality rate of PCP infection is up to 60%.[5]

We report a patient who recently survived paraquat intoxication and presented with acute respiratory insufficiency post glucocorticoid and cyclosporine treatment. PCP infection was confirmed by a PCP deoxyribonucleic acid (DNA) test. The symptoms improved markedly after TMP-SMX treatment.

Case Report

A 36-year-old female presented with progressive shortness of breath for 2 days at Emergency Department (ED). Reviewing her past history, she had been discharged from Nephrology ward 2 weeks before. She had drunk 5 mL of paraquat after quarreling with her husband 3 months earlier. She underwent a complete course of hemoperfusion combined with cyclosporine and steroid pulse therapy during last admission. The steroid dose was tapered to cortisone acetate 25 mg twice daily during outpatient follow-up 4 days earlier and no discomfort was found.

The patient’s dyspnea progressed rapidly and persisted at rest 2 days before admission. Associated symptoms included a dry cough and mild fever. There were no chills, night sweats, weight loss/gain, chest pain, palpitations, decreased urine output, gastrointestinal upset, bowel habit change, skin rash, or leg edema. In the ED, the patient appeared acutely ill and showed air hunger. The initial vital signs were body temperature 36.9°C, pulse 111 per minute, respiratory rate 30 per minute, and oxygen saturation 88% by pulse oximetry on a oxygen flow of 6 L/min via mask. The physical examination showed bilateral crackles in the inspiratory phase. The patient was breathing laboriously with subcostal retraction and accessory muscle use. There was no jugular vein engorgement or peripheral edema. The chest X-ray revealed bilateral perihilar infiltration and a reticular interstitial pulmonary pattern (Figure 1).

Figure 1. Initial chest X-ray at emergency department.

The laboratory evaluation included white blood cell count 9,800/μL (normal 3,500-11,000/μL), bands 11%, lymphocyte 24%, platelets 243,000/μL (150-400 K/μL), C-reactive protein 141 mg/L (< 5 mg/L), procalcitonin 1.1 ng/mL (< 0.5 ng/mL, ≥ 2 Sepsis Likely, ≥ 10 Sepsis), lactate dehydrogenase 721 U/L (125- 225 U/L), aspartate transaminase 928 U/L (< 34 U/L), alanine transaminase 702 U/L (< 36 U/L), total bilirubin 0.5 mg/dL (< 1.3 mg/dL), blood urea nitrogen 15.5 mg/dL (6-21 mg/dL), and creatinine 0.86 mg/dL (0.44-1.03 mg/dL). An HIV test was negative.

The initial impression of this patient was pneumonia complicated with hypoxic respiratory failure. Empirical antibiotic treatment with Tienam (imipenem/ cilastatin) and Teicoplanin was started in the ED. The respiratory pattern deteriorated despite high-flow oxygen by mask.

To treat a possible PCP infection, TMP-SMX 15 mg/kg/day in a divided dose was started on admission to the Intensive Care Unit (ICU) with adjunctive methylprednisolone 40 mg twice daily. The symptoms improved markedly and follow-up chest X-rays on 2 and 7 days after admission revealed resolution of the lung infiltration (Figure 2). A second PCP DNA test confirmed the diagnosis. She was transferred to a general ward on day 3 and discharged 2 weeks later on oral TMP-SMX for the complete treatment.

Figure 2. Follow-up chest x-rays on the second day (A) and the seventh day (B) after admission.

Discussion

There are several aspects should be mentioned. First, this case echoed previous studies with a nonspecific and insidious presentation, with the symptoms being dyspnea and a non-productive cough at ED visit.[6] However, a rapidly progressive clinical course, and a clear medical history of immunocompromised state draw physician’s attention to the possible opportunistic lung infection.[7,8] Coyle et al. performed a retrospective review of PCP in Northern Ireland, and found a rising incidence of PCP of iatrogenic exposure related immune-compromised patients.[9] PCP in patients without acquired immunodeficiency syndrome had been reported before. The risk factor for PCP in patients without HIV infection is defects in cell-mediated immunity.[7,10] A case series in 1996 demonstrated a median prednisolone equivalent dose of 30 mg daily for a median duration of 12 weeks among PCP in patients without acquired immunodeficiency syndrome.[8] The author made the conclusion about steroid used increasing risk of PCP infection due to 90.5% patient used steroid within 1 month before the diagnosis of PCP. Lower lymphocyte counts (< 750 cells/mm³) and high prednisolone dosage (mean 49 mg/day) were considered as other risk factors of PCP infection.[11] Our patient received a mean prednisolone equivalent dose of 100 mg/day for 82 days and absolute lymphocyte counts 2,352 cells/mm³. Therefore, she was susceptible to the PCP infection.

Second, the findings of the plain film in patients with PCP pneumonia are mostly non-specific or inconclusive. [12] In contrast, the chest X-ray of this case showed a perihilar infiltration, and a reticular interstitial pattern, which was highly suggestive of PCP in profound immunocompromised patients.[13] Opravil et al. reported a 36% of interstitial and 25% acinar infiltrates of the radiographic presentation of PCP in 93 consecutive patients.[13] Besides, the mortality was correlated with the severity of infiltrates.[9]

Third, paraquat intoxication causes oxidative damage of the alveolar epithelium with subsequent obliterating fibrosis.[14] One review collect 9 case reports in Spain found PCP infection in an immunocompetent patient after paraquat spraying.[15] It would be interesting to determine whether Pneumocystis can easily penetrate and proliferate after attaching to alveolar epithelium damaged by paraquat.

Conclusion

This report suggests that clinicians should consider PCP infection in patients who develop secondary pneumonia after paraquat intoxication. PCP treatment as part of empirical antibiotics should be added, especially in such patients presented with rapidly progressive course.