Hydroxyurea-induced Pneumonitis in a Patient with Chronic Myelomonocytic Leukemia: An Autopsy Case

Abstract

We describe the case of an 85-year-old man diagnosed with chronic myelomonocytic leukemia whose disease was treated with hydroxyurea for 3 months. He developed respiratory symptoms that were extensively investigated. Despite the intensive treatment, he died of respiratory failure eleven days later. An autopsy revealed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. A drug lymphocyte stimulation test was positive for hydroxyurea. Taken together these findings demonstrated that severe interstitial pneumonitis was induced by this drug. Physicians using hydroxyurea must be aware of its potentially life-threatening pulmonary toxicity.

Fibrotic Lung Toxicity Induced by Hydroxycarbamide

“…This is a rare event and very few cases have been reported in the literature (5)(6)(7)(8)(9)(10)(11)(12). In this limited population, the interstitial lung toxicity generally occurred after a few weeks of exposure to hydroxyurea (9), while in our patient after 15 weeks.…”

“…As previously found by Cleverley et al (13) in a similar case, fever was absent in our patient while dyspnea was severe, the lung toxicity was mainly documented by CT scan alterations and discontinuing hydroxyurea resulted in the improvement of clinical and radiological conditions. However, hydroxyurea-induced pneumonia was reported as being lethal in a recent case report in which steroids were also used at high dose with no benefit; the disease diagnosis was confirmed after autopsy and by a drug lymphocyte stimulation test positive for hydroxyurea (11).…”

“…As suggested by Rossi et al (8) and others (11)(12)(13), the identification of ground-glass opacities at high resolution CT scan of the chest in a patient with acute respiratory symptoms treated with hydroxyurea requires a complex differential diagnosis with bacterial or viral pneumonitis, respiratory infections (aggravated by myelosuppressive therapy), and pulmonary hypertension. In our patient, the microbiological examinations allowed for exclusion of infections and the radiological high-resolution CT features were consistent with the phenomenon of drug-induced lung toxicity being similar to an hypersensitivity pneumonitis-like pattern and comparable to a histological picture of diffuse alveolar damage, already reported in Pneumotox associated with hydroxyurea exposure (14).…”

Hydroxyurea-Induced Pneumopathy in a Patient With Myeloproliferative Syndrome

“…These present in a similar way to the aforementioned case both in symptoms (fever, dry cough, absence of respiratory secretions) and radiological findings (diffuse alveoli-interstitial infiltrates in lung fields) The findings observed in CT show more variability, with the predominance of tarnished glass or panalization patterns, bilateral interstitial infiltrates, and reticulonodular opacities. [1][2][3]5 To our best understanding, only 5 cases with anatomopathologic study compatible with HU pneumonitis have been described in the literature. In these cases, samples were obtained with transbronchial biopsy (1 case), lung biopsy (3 cases), or autopsy (1 case).…”

Potential Amelorative Effect of Panax Ginseng on Hepatorenal Damage Ocuured in Hydroxurea-Treated Rats

“…Cardiovascular effects and slight methemoglobinemia were detected in some species ''at doses higher than clinical levels'' (13,16), skin and nail lesions have been reported in human and canine patients (2,17,18). In addition, HU can induce lung toxicity with pulmonary edema, lung infiltration and dyspnea (19), and pulmonary fibrosis in a minority of patients (20).…”