A 16 Year Old Girl With A Past History Of Chemotherapy Presents With Breathlessness.

A 16 year old girl who had a past history of acute myeloid leukemia and was treated with six courses of chemotherapy presents to her doctor with the complain of Breathlessness on exertion. During her chemotherapy she was also given cyclophosphamide. On examination patient appears to be breathless even at rest and she looks cyanosed. There is no evidence of clubbing. Her lung function test shows FEV1/FVC ratio of 80%, but there is a decreased total lung capacity, indicating a restrictive pattern.
Her chest X ray is shown below:

The X ray shows diffuse infiltrates indicative of interstitial lung disease.

What is the cause of patient's symptoms in the above mentioned case?

Answer: Cyclophosphamide induced lung fibrosis.

Case Discussion:
Cyclophosphamide induced lung fibrosis is a relatively rare condition and is most likely to occur in patients who had concomitant pulmonary radiation or has taken other drugs that are toxic to the lungs. Patients may present several years after the cessation of treatment and with advanced damage to the lungs.
The diagnosis is usually clinical from the history of exposure to the drug and from restrictive lung defect on pulmonary function test. The chest X ray shows reticulonodular shadowing more so in the upper zones.

Cyclophosphamide per se is not toxic to the lungs, instead it is metabolized in the liver to hydroxycyclophosphamide, acrolein and phosphoramide mustard which are responsible for the pulmonary damage.

The other drugs that may cause pulmonary fibrosis include:

• Busulphan
• Methlysergide
• Methotrexate
• Amiodarone
• Nitrofurantoin
• Ethambutol
• Minocycline
• Penicillamine.