Original case provided by Lauren Brown, MD.
Edits, teaching points and graphics by Yilin Zhang, MD.
- Recognize pulmonary complications of amiodarone
A 77 yo M with a history of atrial fibrillation, nonischemic cardiomyopathy (EF 40%) presents with 3 weeks of nonproductive cough and exertional dyspnea. He feels he “can’t take a deep breath” but denies any chest pain, orthopnea, LE edema. He denies URI symptoms, fevers/chills or recent sick contacts. At baseline, he is able to walk several miles without difficulty and now is limited to < 1 city block.
His PMH is notable for paroxysmal atrial fibrillation status post ablation for which he has been on warfarin and amiodarone for several years. He has an AICD for his history of cardiomyopathy. He previously smoked 30 pack years but quit several years ago. He has lived all around the US but denies international travel. He has 2 dogs at home and denies any other pet exposures.
What is your differential for these CXR findings?
- Volume overload (especially with history of NICM)
- Multifocal pneumonia
- Interstitial lung disease
What is your differential for this CT finding?
NSIP is typically associated with collagen vascular diseases (e.g., scleroderma, dermatomyosis), drug-induced lung injury or hypersensitivity pneumonitis. Given his long amiodarone history, amiodarone lung toxicity is the most likely diagnosis.
Other possibilities could be infection or pulmonary edema superimposed on interstitial lung disease.
OUTCOME AND FINAL DIAGNOSIS:
He underwent inpatient PFTs (see additional learning section) and TTE, which showed stable cardiac function with EF Of 44% without signs of intravascular volume overload. He underwent bronchoscopy which ultimately revealed 1.7 million WBCs (95% eosinophils), infectious work-up was otherwise negative. This was thought to be consistent with amiodarone induced pulmonary toxicity with pulmonary eosinophilia (acute eosinophilic pneumonia versus chronic eosinophilic pneumonia). His amiodarone was stopped and he was started on prednisone 40 mg daily with a prolonged taper. CXR a year later showed resolution of fibrosis.
He underwent inpatient PFTs (see additional learning section) and TTE, which showed stable cardiac function with EF Of 44% without signs of intravascular volume overload. He underwent bronchoscopy which ultimately revealed 1.7 million WBCs (95% eosinophils), infectious work-up was otherwise negative. This was thought to be consistent with amiodarone induced pulmonary toxicity with pulmonary eosinophilia (acute eosinophilic pneumonia versus chronic eosinophilic pneumonia).
His amiodarone was stopped and he was started on prednisone 40 mg daily with a prolonged taper. CXR a year later showed resolution of fibrosis.
What effect does amiodarone have on the lung?
Most effects of amiodarone on the lungs are due to tissue accumulation with long term oral therapy. There are several forms of pulmonary disease2:
- Interstitial pneumonitis (usually after several months with NSIP histologic pattern)
- Characteristic finding of “foamy macrophages” from amiodarone-phospholipid complexes can be seen in up to 50% of amiodarone exposed lungs along without associated pneumonitis2
- Organizing pneumonia
- ARDS (rare)
- Diffuse alveolar hemorrhage (rare)
- Pulmonary modules or mass (case reports and case series)
- Pleural effusion is exceedingly (rare)
The mechanism is not well understood but is thought to be 2/2 to direct toxic effect to the lung and hypersensitivity immunologic reaction.
How is it diagnosed?
Gold standard is a histologic diagnosis. However, most commonly, the diagnosis is made clinically with the following2:
Stopping amiodarone and prolonged high dose systemic steroids (typically for 4-12 mos) for symptomatic patients are the cornerstones of therapy. Because amiodarone has such a long half life, there may be clinical worsening before improvement and recovery can take several months.
What were our patient’s risk factors?
- High cumulative dose of amiodarone – patients at risk are on
- > 200 mg/d for >1 year
- >400 mg/d for > 2 months are at highest risk
Patients with underlying lung disease are also at risk (though our patient did not have this)
Can he be restarted on amiodarone after resolution of their pulmonary symptoms?
No. There is a risk of recurrent lung disease and progressive pulmonary fibrosis.
Our patient required additional antiarrhythmic therapy and was subsequently trialed on dronedarone and dofetilide rather than amiodarone given risk of pulmonary toxicity.
TAKE HOME POINTS:
- CT imaging plays a central role in diagnosis in the right clinical context, which most commonly shows an interstitial pneumonitis (typically with nonspecific interstitial pattern)
- Patients at risk are those with high cumulative doses of amiodarone and are typically on amiodarone for several months prior to onset of symptoms
- Treatment is with withdrawal of amiodarone and high dose steroids.
Our patient additionally underwent PFTs as part of his work-up which showed:
|2.2 L (65% predicted)
3.3 L (74% predicted)
5.29 (75% of predicted)
1.5 L (61% predicted)
How would you interpret these PFTs? (~5 min)
1. FEV1/FVC ratio <0.7 (Gold criteria) is suggestive of obstructive lung disease
- Severity of obstructive defect is determined by FEV1 – 65% of predicted is suggestive of mild-moderate obstructive disease
- Of note, ATS/ERS criteria for obstruction is slightly different: <0.08 predicted in men, < 0.09 predicted in women
2. Decreased FVC and TLC is suggestive of restrictive disease
- FVC or TLC predicts severity of restrictive disease – 74% of predicted is consistent with mild restriction
- Decreased DLCO is typically consistent with parenchymal disease/ fibrosis, but can also be seen in pulmonary vascular diseases).
- There is mixed mild-moderate obstructive and mild restrictive defect.
What other organs are affected by amiodarone? (~ 5 min)
Adapted from Table 2: Adverse extrapulmonary effects of amiodarone (Wolkove & Baltzan, 2009)
- Kadoch, MA, et al. Idiopathic Interstitial Pneumonias: A Radiology-Pathology Correlation Based on the Revised 2013 American Thoracic Society-European Respiratory Society Classification System. Current Problems in Diagnostic Radiology. 2015; 44(1): 15-25.
- Wolkove, N & Baltzan, M. Amiodarone pulmonary toxicity. Canadian Respiratory Journal. 2009; 16(2): 43-48.